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Allergy 04/2007; 8(3):181 - 188. · 6.27 Impact Factor
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ABSTRACT: In the present study we describe the molecular analysis of c-Ha-ras gene mutations in 47 papillomas and 17 carcinomas developed in two lines of mice, carcinogenesis-susceptible (Car-S) and carcinogenesis-resistant (Car-R), selectively bred for extreme susceptibility or resistance to chemical skin carcinogenesis initiated and promoted with different doses of 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). This study also presents the analysis of c-Ha-ras gene mutations in 22 papillomas and 22 carcinomas in Car-S mice initiated with DMBA and promoted with benzoyl peroxide (BzPo) and in seven papillomas and one carcinoma from a group of uniniated Car-S mice that received only BzPo treatment. The data showed that a A(182)-->T transversion in the c-Ha-ras gene was present in 100% and 81% of the skin tumors developed in Car-S and Car-R mice, respectively, after DMBA initiation and TPA promotion, suggesting that differences in genetic susceptibility can influence the frequency of c-Ha-ras mutations in the skin tumors produced. The same A(182)-->T mutation with an incidence of 68% was found in papillomas from DMBA-initiated and BzPo-promoted Car-S mice. The difference in the mutation frequency between DMBA/BzPo and DMBA/TPA papillomas suggested that the promotion step contributes to the final mutation pattern. The tumor induction experiment with BzPo alone showed that this compound can induce tumor development in 26% of Car-S mice, and the molecular analysis of the tumors showed a broad mutation spectrum, including mutations in codons 12, 13, and 61 of the c-Ha-ras gene. Mol. Carcinog. 30:111-118, 2001.
Molecular Carcinogenesis 03/2001; 30(2):111-8. · 3.16 Impact Factor
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ABSTRACT: We report on bidirectional selective breeding, initiated from a genetically defined foundation population and carried out to selection limit, for producing lines of mice endowed with maximal resistance (Car-R) or maximal susceptibility (Car-S) to 2-stage skin tumorigenesis. The initial population resulted from a balanced intercrossing of 8 inbred strains of mice. The tumors, induced by a single application of DMBA (initiation) and twice weekly applications of TPA (promotion), were benign papillomas; their number at the end of the promotion period was the phenotype chosen for assortative mating. Afterward, the majority of them regressed while others progressed to malignant carcinomas. The Car-R line was selected through a strong challenge, while the Car-S line selection was based on responses to decreasing concentrations of DMBA and TPA. The selection limit was reached after 14 or 15 generations showing progressive interline divergence, which strongly suggests the interaction of several quantitative trait loci (QTL). The phenotypic difference was extremely large: the tumor response was 73 times higher in Car-S than in Car-R mice, though the applied concentrations of DMBA and TPA were 100 and 40 times lower, respectively. The mean heritability realized during the selective breeding was 0.20 in Car-R and 0.49 in Car-S. Our results are compatible with a minimal QTL estimate of 8 in the Car-R line and of 9 or 10 in the Car-S line. The Car-S line is also much more susceptible to carcinoma induction. An association of coat color with tumorigenesis was observed in interline F2 segregants. The Car-R and Car-S lines, obtained through a long-lasting breeding program, are a unique model for identifying the QTL involved in chemical tumorigenesis and will be provided to interested investigators.
International Journal of Cancer 12/2000; 88(3):424-31. · 5.44 Impact Factor
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ABSTRACT: Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice were obtained applying a bi-directional selective breeding approach to a two-stage skin carcinogenesis protocol, using 9,10-dimethyl-1,2-benzanthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. Sixteen generations of selection produced a remarkable interline difference in responsiveness to two-stage skin carcinogenesis between Car-R and Car-S: identical DMBA (25 microgram) and TPA (5 microgram) doses induced papillomas in 100% of Car-S compared with 3.3% of Car-R mice and maximal responses of 14.3 or 0.03 papillomas/mouse, respectively, despite the shorter promotion applied to Car-S (49 vs. 208 days). To define the factors determining this great difference, Car-R and Car-S mice were challenged by initiators/promoters chemically unrelated to those used for selection. Both lines were subjected to either initiation by N-methyl-N-nitrosourea (MNU) followed by TPA promotion, or promotion by benzoyl peroxide, or 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) following DMBA initiation. Initiation with MNU induced a 10-fold tumour incidence in Car-S compared with Car-R mice, and a 32-fold difference in tumour induction rate. The 2 lines also differed markedly in susceptibility to benzoyl peroxide promotion: Car-S mice initiated with 25 microgram DMBA and promoted with 7.5 mg benzoyl peroxide showed a 12-fold tumour incidence and a 103-fold tumour induction rate compared with the corresponding Car-R group. Both lines, however, were refractory to chrysarobin promotion. The progression of papillomas to carcinomas was examined in all Car-S groups. The incidence of mice that developed carcinomas was 57% in MNU-initiated mice. Benzoyl peroxide was also able to promote carcinoma development in Car-S mice, though with a lower incidence (30.4%) than TPA.
International Journal of Cancer 11/1999; 83(3):335-40. · 5.44 Impact Factor
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ABSTRACT: High and low antibody responder lines of mice from Selections I, III and G were assayed for two-step skin tumorigenesis using a protocol consisting in initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Concordant results were obtained in the three selections: low antibody responder mice were shown to be significantly more resistant to tumor induction than the high responder counterparts. The difference was observed for all parameters: kinetics and percentages of tumor incidence and tumor multiplicity. The three bidirectional selective breeding experiments differed in several respects namely, the origin of the foundation populations, the antigens and immunization protocols used during the selection, as well as the breeding unit environments. Therefore, the consistent results relative to tumorigenesis strongly suggest that some of the alleles relevant to multispecific 'low' antibody production could contribute to the resistance to cutaneous chemical tumorigenesis.
Cancer Letters 04/1999; 136(2):153-8. · 4.24 Impact Factor
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G Biozzi,
O G Ribeiro,
A Saran,
M L Araujo,
D A Maria,
M De Franco,
W K Cabrera,
O A Sant'anna,
S Massa,
V Covelli,
D Mouton,
T Neveu,
M Siqueira,
O M Ibanez
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ABSTRACT: Two distinct bidirectional selective breedings for quantitative traits were initiated from identical genetically heterogeneous mouse populations. The resulting lines are characterized by maximal or minimal acute inflammatory responsiveness (AIR): AIRmax and AIRmin lines, respectively, and by resistance or susceptibility to chemical skin tumorigenesis: Car-R and Car-S lines, respectively. The AIR response to s.c. injection of polyacrylamide microbeads, measured by cell content in the local exudate, was 10 times higher in AIRmax than in AIRmin mice. The response to selection was asymmetrical: the realized heritability was 0.26 in AIRmax and 0.008 in AIRmin, and resulted from the additive effect of 7-11 quantitative trait loci (QTL). Low responsiveness was globally dominant in F1 and 48% of F2 segregant variance was found to be due to genetic factors. These findings are the first demonstration of innate regulation of AIR by germ line genes. Susceptibility to skin tumorigenesis induced by a two-stage initiation (DMBA)-promotion (TPA) protocol was lower in AIRmax mice than in AIRmin mice, a 6-fold difference in tumor induction rate. Intense AIR was found to be associated with resistance, and low AIR with susceptibility to tumorigenesis, in F2 segregants chosen for extreme AIR phenotypes. At least some of the AIR QTLs therefore contain genes controlling tumorigenesis. Tumor phenotypes differed more in Car-R and Car-S than in AIRmax and AIRmin lines, indicating that QTLs unrelated to AIR, contribute to the host response to tumorigenesis. The extreme phenotypes/genotypes of the four selected lines and the known genetic constitution of their foundation population, offer new possibilities to discriminate the genes/mechanisms controlling two important traits: AIR and response to chemical tumorigenesis. Collaborative projects will be favorably considered. The description of tumor resistance genes in AIRmax and Car-R mice may be helpful for epidemiology and therapy of human cancer.
Carcinogenesis 03/1998; 19(2):337-46. · 5.70 Impact Factor
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ABSTRACT: Age-related alterations of the immune system affect both antibody and cell-mediated immune responses, T-cell responses being more severely affected than B-cell responses. Within the T-cell population, aging leads to replacement of virgin by memory cells and to accumulation of cells with signal transduction defects. Changes in T-cell subsets and in cytokine production profiles may produce suitable conditions for T-cell-mediated disregulation of antibody responses characterized by the production of low affinity and self-reactive antibodies. Also B-cells exhibit intrinsic defects and natural killer (NK) cell activity a profound loss in old mice. Whether age-related immune disfunctions influence life span and tumor incidence has been examined in mice genetically selected for high or low antibody responsiveness. It has been found that genetic selection of vigorous antibody responses in most cases produces mice with longer life span and lower lymphoma incidence. Moreover, the results of genetic segregation experiments indicate that antibody responsiveness and life span are polygenic traits regulated by a small number of the same or closely linked loci. Mice genetically selected for high or low mitotic responsiveness to PHA exhibit low or high tumor incidence, respectively, but no difference in life span, suggesting that T-cell activity is restricted to immune surveillance of neoplastic transformation. Studies on mice genetically selected for resistance or sensitivity to chemical carcinogenesis have uncovered loci that control both resistance to tumor induction and longevity while have no effects on immunity and disease incidence. Thus, the relative role of the immune system in conditioning the duration and the biological quality of life remains to be determined.
Mechanisms of Ageing and Development 07/1997; 96(1-3):1-13. · 3.44 Impact Factor
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ABSTRACT: Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice have been obtained by the method of bi-directional selective breeding. After 10 generations of selection Car-R and Car-S mice show a remarkable difference in their response to chemical carcinogenesis. Car-R and Car-S mice, initiated and promoted by skin application of 9,10-dimethyl-1,2-benzanthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) reach a tumour multiplicity of 0.05 and 6.2, respectively, after 49 days of promotion. When benzo[a]pyrene (B[a]P) is topically applied for initiation, followed by TPA promotion, Car-R and Car-S mice maintain a large difference in sensitivity to skin tumour induction. Car-S mice are also more susceptible than Car-R mice to complete carcinogenesis produced by single or repeated applications of DMBA only. On the contrary, when DMBA or B[a]P are administered by subcutaneous injection rather than by topical application, no significant difference in tumour incidence is observed between the two lines. All tumours induced by topical administration of carcinogens on the skin are of epithelial origin, whereas the tumours produced by subcutaneous injection are of connectival origin. These observations suggest a tissue-specific effect of the selected genes, probably restricted at the skin level.
Carcinogenesis 12/1996; 17(11):2463-8. · 5.70 Impact Factor
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ABSTRACT: Susceptible (Car-S) and resistant (Car-R) lines of mice separated by 10 consecutive generations of bidirectional selective breeding present a very large difference in responsiveness to two-stage skin carcinogenesis. Car-S mice initiated with 0.5 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA) and promoted with 0.25 micrograms 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 77 days showed a papilloma incidence of 88% and a tumour multiplicity of 3.2 +/- 0.4 (mean +/- SE), with a tumour induction rate of 0.415. Car-R mice initiated with larger DMBA and TPA doses (50 micrograms and 20 micrograms respectively) and promoted for 111 days gave a comparable papilloma response: incidence 65%, tumour multiplicity 3.2 +/- 0.6 and tumour induction rate 0.288. The difference in papilloma response between the two lines is due to the interaction of genetic and environmental factors. In order to overcome the genetic effect with environmental factors and induce in Car-R a papilloma response comparable to that of Car-S, the DMBA dose had to be increased up to 100 times, that of TPA 40 times and the promotion time augmented by 44%. Papilloma to carcinoma conversion 112 days after the end of promotion depends on the DMBA and TPA doses applied. The number of carcinomas induced in Car-S mice and in (Car-S X Car-R) F1 hybrids was larger than that induced in Car-R mice, but the ratio of carcinoma conversion was lower, therefore a larger proportion of the small number of papillomas induced in the Car-R mice progressed to malignancy. The dominance effect measured in (Car-S X Car-R) F1 hybrids demonstrated that the susceptibility to papilloma induction was an incomplete dominant character (d/a = 0.38), whereas for carcinoma conversion the resistance was incompletely dominant (d/a = -0.49).
Carcinogenesis 12/1994; 15(11):2629-35. · 5.70 Impact Factor
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ABSTRACT: Two lines of mice were produced by bidirectional selective breeding: one resistant (CAR-R) and one susceptible (CAR-S) to two-stage skin carcinogenesis by dimethylbenz(a)anthracene and 12-O-tetradecanoyl-phorbol-13-acetate. The dimethylbenz(a)anthracene-DNA adduct formation was compared in the two lines by a postlabeling procedure so as to determine whether the striking interline difference observed as to tumor incidence could (in part) be due to differences in the formation of DNA-reactive metabolites. Results show that qualitatively, adduct profiles in CAR-R and CAR-S epidermis are similar. Quantitatively, the total binding level is slightly higher in CAR-S versus CAR-R mice during the 30-day follow-up. However, these minor differences do not increase in function of the response to selection observed through three consecutive generations. A 2- or 4-week promotion with 12-O-tetradecanoylphorbol-13-acetate enhances the decrease of adduct level in the two lines. This effect is somewhat more pronounced in CAR-S mice. Results strongly suggest that the expression of the genes responsible for CAR-R/CAR-S phenotypic difference affects mainly the postinitiation stages.
Cancer Research 10/1994; 54(17):4635-40. · 7.86 Impact Factor
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ABSTRACT: Six generations of a bidirectional selective breeding model for producing lines of mice susceptible (Car-S) and resistant (Car-R) to two-stage skin carcinogenesis are described. Initiation was with 9,10-dimethyl-1,2-benzanthracene (DMBA single application), and promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA twice weekly). The selective breeding was initiated with a highly genetically polymorph foundation population, produced by the intercrossing of eight inbred mouse strains. The Car-S line was produced by assortative mating of the mice presenting the largest number of tumors induced by low DMBA and TPA doses, the Car-R line by mating tumorless mice or mice showing the smallest number of tumors induced by large DMBA and TPA doses. The character investigated was expressed as per cent tumor incidence and as tumor multiplicity per mouse. The mean heritability of the susceptibility character for the two first generations was 0.84 for tumor incidence and 1.3 for tumor multiplicity; these values decreased to 0.53 and 0.44 respectively for the two consecutive generations. The heritability of the resistance character maintained a constant value of 0.29 +/- 0.04 for tumor incidence, and 0.53 +/- 0.08 for tumor multiplicity. The progressive response to selection indicates that the characters investigated are subject to polygenic regulation, even though some genes may have a major effect on the susceptibility character. The interline separation in F5, challenged with the same initiation and promotion schedule, is very large. In the Car-S line, tumor incidence was 82.5% and tumor multiplicity 4.9/mouse on promotion day 49, whereas the corresponding values for the Car-R line were 4.5% and 0.1/mouse on promotion day 81.
Carcinogenesis 11/1990; 11(10):1711-9. · 5.70 Impact Factor
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ABSTRACT: Acute inflammation is induced by the subcutaneous injection of swollen polyacrylamide microbeads, its intensity measured by the cell and protein concentration of the local exudates. A large and continuous range of responses is obtained in different inbred strains of mice, which suggests a polygenic control of the inflammatory response. The variable levels of the global dominance observed in F1 hybrids issued from several parental combinations indicated that the pattern of alleles controlling high or low response was different in each parental strain. Balanced intercrossing of the 8 inbred strains studied has provided a genetically heterogeneous F3 population, presenting a high variability of responses. The value of the genetic part of F3 phenotypic variance, the spread of the interstrain differences, as well as the polygenic nature of the regulation of inflammatory responses pointed out the possibility to perform a bidirectional genetic selection by using the F3 mice as the foundation population, and response to microbeads as the selective phenotypic character.
Experimental and Clinical Immunogenetics 02/1990; 7(4):221-33.
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ABSTRACT: High (H) and low (L) antibody responder lines of mice separated by selective breeding present a maximal interline difference in antibody (Ab) response to Ag of different specificities (general genetic regulation). The analysis of SRBC agglutinin response in H line, L line, F1 hybrids, F2, and backcross segregants demonstrates that Ab responsiveness is a polygenic trait regulated by the additive interaction of 5 to 7 independent loci, with an incomplete dominance (44% +/- 7%) of the high response character, and a 30% +/- 10% impact of the environmental factors. The life span of H, L, F1, F2, and backcross populations is correlated positively with 2-ME-resistant agglutinin response (r = 0.97, p less than 0.001) and negatively with 2-ME-sensitive agglutinin response (r = 0.95, p = 0.01) (interpopulation correlation). Similar correlations are also observed in individuals of the various populations, especially in F1 x L backcross, in which the largest phenotypic variance is found. The positive correlation between Ab responsiveness and life span was confirmed by ELISA titration for distinct IgG isotypes (intrapopulation correlation). Malignant lymphomas and chronic nephritis were the two most common diseases observed. The age-adjusted incidence of such diseases, which is largely affected by environmental factors, accounts for the longer life span of H, as compared with L, mouse populations. The longevity of the 30% or less survivors, chiefly determined by the rate of physiologic aging, is a polygenic character regulated by the cumulative interaction of 3 to 7 independent loci, with a complete dominance of the long life trait and an impact of the environmental factors of about 60%. Thus we have grounds for regarding general Ab responsiveness and life span as polygenic traits regulated by a small number of identical or closely linked gene loci, and immune responsiveness as a defense mechanism against neoplastic and inflammatory diseases.
The Journal of Immunology 03/1989; 142(4):1224-34. · 5.79 Impact Factor
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ABSTRACT: Bi-directional selective breeding for antibody (Ab) responsiveness to heterologous erythrocytes (Selection I) produced a high (H) and a low (L) responder line of mice which were also remarkably separated for Ab responses to many unrelated natural antigens (Ags) such as heterologous proteins, viruses, bacteria, parasites and haptens carried by these immunogens. The character "quantitative Ab responsiveness" is controlled by several independently segregating loci (polygenic regulation). The major genetic modification is produced at the level of macrophage activities. The Ag is slowly catabolized and persists for a long time on the macrophage membrane of the H line, whereas it is rapidly destroyed in L line macrophages. The bactericidal and bacteriostatic activity of the macrophage is also strong in the L line and weak in the H line. The opposite genetic regulation of Ab responsiveness and macrophage activity is a fundamental phenomenon for understanding natural and vaccination-induced anti-infectious immunity. The L line is more resistant than the H line against the infections due to intracellular microorganisms (Salmonellae, Yersinia, Mycobacteria, Brucellae, Leishmania) where the macrophage plays the dominant defensive barrier. The H line is more resistant than the L line to the extracellular microorganisms which are efficiently counteracted by a strong antibody response (Pneumococcus, Klebsiella, Plasmodia, Trypanosoma). The intensity of T cell-mediated immunity as measured by delayed type hypersensitivity, which is independent of the genetic regulation of antibody responsiveness, is correlated with the degree of nonspecific inflammation produced at the site of the reaction by the Ag injection in non-sensitized mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunology Letters 01/1988; 16(3-4):205-17. · 2.53 Impact Factor
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ABSTRACT: The selective breeding for antibody production against bovine serum albumin (BSA) and rabbit gamma-globulin (RGG) induced a large modification in responsiveness in the high (Hv) and low (Lv) responder lines at selection limit. The total response to selection (RT) was 9.0 log2 for BSA and 8.4 log2 for RGG. This gives an interline difference of 500-fold and 337-fold respectively in terms of passive agglutinin titres. For BSA responsiveness, there is, in F1 interline hybrids, an incomplete dominance effect of the low character (-0.41) and a marked maternal effect. Complete dominance effect of high character (1.08) without any maternal effect is observed for responses to RGG. The phenotypical variability of BSA responses in F2 segregants is due 60% to genetic factors and 40% to environmental effects. Such a distribution cannot be achieved for RGG responsiveness. Both responses to BSA and RGG are controlled by the additive effect of several independent loci (polygenic regulation). One of these genes is linked with the H-2 locus. The H-2 linked gene accounts for 29% of the total interline difference for response to BSA and only 11% for response to RGG. Experiments carried out to measure the reciprocal nonspecific effect of BSA and RGG responses failed to give clear-cut results. This important phenomenon will be the subject of the companion article.
Experimental and Clinical Immunogenetics 02/1986; 3(3):162-71.
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ABSTRACT: In order to measure the reciprocal nonspecific effect of the genetic regulation of antibody responsiveness to bovine serum albumin (BSA) and rabbit gamma-globulin (RGG), two independent bidirectional selective breedings for responses to these two antigens were carried out: selection V/BSA and selection V/RGG respectively. The total interline separation at selection limit (RT) was 5.3 log2 for selection V/BSA and 2.6 log2 for selection V/RGG. The sum of these two values (7.9 log2) is similar to the RT in selection V carried out by alternating these two antigens in consecutive generations. In selection V/BSA, the nonspecific effect for responsiveness to RGG was 72%. In selection V/RGG, the nonspecific effect for BSA responsiveness was 135%. The F1 hybrids between homologous lines of selection V/BSA and selection V/RGG presented a larger difference in antibody response to both antigens than their parental lines. This demonstrates an additive effect of the loci controlling the two responses.
Experimental and Clinical Immunogenetics 02/1986; 3(3):172-80.
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ABSTRACT: The genetic modifications of immunocompetent cell functions were investigated in high (H) and low (L) antibody responder lines of mice obtained by selective breeding for responsiveness to flagellar and somatic antigens of Salmonellae (Selection III and Selection IV, respectively). Several lines of evidence converge to demonstrate that the differences in antibody responses between the H and L lines of the two selections are not due to the modification of antigen handling by macrophages. This contrasts with previous observations that macrophages play a major role in interline differences in Selections I and II. The choice of antibody titres after secondary challenge as the phenotypic character in Selections III and IV may explain why the regulatory role of macrophages was minimized, compared with Selections I and II which were carried out for primary responses to heterologous erythrocytes. In Selections III and IV, H mouse lymphocytes were more efficient than L mouse lymphocytes in restoring immunoresponsiveness to irradiated hosts. In contrast, allogeneic skin grafts were rejected at a similar rate in L as well as in H mice of the two Selections and in vitro lymphoproliferative responses to T cell mitogens were also equivalent in the four lines.
Journal of immunogenetics 01/1986; 12(6):309-19.
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ABSTRACT: Resistance to Toxoplasma gondii infection was studied in the high (H/f) and low (L/f) antibody responder lines of mice that were selected on the basis of quantitative antibody responsiveness to the flagellar antigen of Salmonella (selection III). No interline difference was observed in resistance to a highly virulent strain of T. gondii. In contrast, H/f mice were much more resistant than L/f mice to a moderately virulent strain of T. gondii: a 5000-fold difference in terms of the 50% lethal dose was found. The degree of resistance in (H/f X L/f)F1 hybrids was intermediate compared with that in parental lines for both mortality and survival time. The antibody titers to Toxoplasma antigens measured during the course of the infection were significantly higher in H/f than in L/f mice. This interline difference was underestimated because parasite multiplication occurs faster in L/f mice, which increases antigenic stimulation. The stronger resistance of H/f mice is probably due to their higher capacity of antibody production in the course of infection.
Infection and Immunity 06/1985; 48(2):298-302. · 4.16 Impact Factor
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ABSTRACT: The resistance to Mycobacterium bovis (BCG) of lines of mice selected for high (H) or low (L) antibody responsiveness was estimated from the rate of BCG multiplication in the organs. During the first 2 weeks after i.v. infection with 5 X 10(6) CFU, BCG multiplied faster in the spleens of H than of L mice. Afterwards there was a more drastic reduction of viable BCG counts in H mice than in L mice so that the residual BCG counts were significantly lower in H mice than in L mice, not only in the spleen but also in the liver and lungs. On the 14th day of infection, the spleen and liver enlargement and the increase of phagocytic activity were similar in the two lines, suggesting an identical T lymphokine release. In contrast with BCG, during the first 2 weeks after infection with 7 X 10(5) CFU, M. tuberculosis (H37Rv) multiplied in the spleens of L mice at a similar or a slightly faster rate than in the spleens of H mice. On the 4th week, the viable H37Rv counts were reduced in H mice whereas L mice did not survive the infection. In mice vaccinated with BCG 5 months before virulent challenge, the multiplication of H37Rv was inhibited in the H and L lines. The protective effect of BCG is therefore stronger in L mice taking into account their higher innate susceptibility to H37Rv. This might be due to the higher level of living BCG found in L mice at the time of challenge.
Clinical & Experimental Immunology 02/1985; 59(1):177-84. · 3.36 Impact Factor
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ABSTRACT: Serum Ig concentration and isotype distribution were determined in the high (H) and low (L) responder lines selected for antibody response to complex immunogens. Data were recorded in normal and postimmunization sera from the H and L lines produced by five independent selective breedings (selections I, II, III, IV, and V). Ig levels were much higher in H than in L mice of all the selections. In four selections this interline difference increased further after immunization with the selection antigens. This is in agreement with the general effect of the polygenic control of antibody responses operating in H and L lines. The Ig isotype profiles of normal sera were different in each line; however, similitudes were noticed between H and L lines in selections I and II. In contrast, in selections III, IV, and V a similar interline difference was observed: the lack of IgG2a isotype in L lines only. After immunization there were minor alterations of the isotype profiles except in the H lines of selections III and IV, in which a clear inverse modification of IgG1 and IgG2a proportions occurred. The characteristic pattern of each selection may be partially dependent on isotype-restricted regulatory effects in relation to the immunization procedure used for selective breeding.
Immunogenetics 02/1985; 22(2):131-9. · 2.93 Impact Factor
