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Clinical dysmorphology 04/2013; 22(2):81-3. · 0.47 Impact Factor
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American Journal of Medical Genetics Part A 03/2013; · 2.39 Impact Factor
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ABSTRACT: Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not
genotoxicin vivo, butin vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test ifin vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin
in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays
were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly
different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin
reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals
exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative
data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than
in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE)
was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of
polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed
to curcumin.In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced
by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by
high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by
copper in the presence of curcumin.
Keywordscomet assay-copper-curcumin-genotoxicity-genoprotection-micronuclei-mouse
Journal of applied genetics 04/2012; 48(4):389-396. · 1.66 Impact Factor
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Clinical dysmorphology 05/2011; 20(4):232-3. · 0.47 Impact Factor
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ABSTRACT: Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not genotoxic in vivo, but in vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test if in vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE) was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed to curcumin. In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by copper in the presence of curcumin.
Journal of applied genetics 02/2007; 48(4):389-96. · 1.66 Impact Factor
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ABSTRACT: Dietary polyphenolics, such as curcumin, have shown antioxidant and anti-inflammatory effects. Some antioxidants cause DNA strand breaks in excess of transition metal ions, such as copper. The aim of this study was to evaluate the in vitro effect of curcumin in the presence of increasing concentrations of copper to induce DNA damage in murine leukocytes by the comet assay. Balb-C mouse lymphocytes were exposed to 50 microM curcumin and various concentrations of copper (10 microM, 100 microM and 200 microM). Cellular DNA damage was detected by means of the alkaline comet assay. Our results show that 50 microM curcumin in the presence of 100-200 microM copper induced DNA damage in murine lymphocytes. Curcumin did not inhibit the oxidative DNA damage caused by 50 microM H2O2 in mouse lymphocytes. Moreover, 50 microM curcumin alone was capable of inducing DNA strand breaks under the tested conditions. The increased DNA damage by 50 mM curcumin was observed in the presence of various concentrations of copper, as detected by the alkaline comet assay.
Journal of applied genetics 02/2006; 47(4):377-82. · 1.66 Impact Factor
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ABSTRACT: Mitotic configurations consistent in split centromeres and splayed chromatids in all or most of the chromosomes or premature centromere division (PCD) have been described in three categories. (1) Low frequency of PCD observed in colchicines-treated lymphocyte cultures from normal individuals. (2) High frequency of PCD with mosaic variegated aneuploidy. (3) High frequency of PCD as a sole chromosome abnormality observed in individuals with no recognizable clinical pattern. We report four members of a family with the third category of PCD.
Cell cycle duration assessed by average generation time using differential sister chromatid stain analysis and FISH studies of DNA centromere sequences in PCD individuals, are included and compared with previously reported PCD individuals from 9 families.
We observed PCD in colchicine-treated cultures from the propositus, his father, and two paternal aunts but not in his mother and four other paternal and maternal family members, as well as in untreated cultures from the propositus and his father. We observed cytological evidence of active centromeres by Cd stain. Significative cell cycle time reduction in anaphases of PCD individuals (average generation time of 21.8 h;SD 0.4) with respect to individuals without PCD (average generation time of 31.8 h;SD 3.9) was observed (P < 0.005, Student t-test for independent samples). Increased cell proliferation kinetics was observed in anaphasic cells of individuals with PCD, by differential sister chromatid stain analysis. FISH studies revealed the presence of alpha satellite DNA from chromosomes 1, 13, 21/18, X, all centromeres, and CENP-B box sequences in metaphasic and anaphasic cells from PCD individuals.
This report examines evidences of a functional relationship between PCD and cell cycle impairment. It seems that essential centromere integrity is present in these cases.
BMC Medical Genetics 09/2005; 6:33. · 2.33 Impact Factor
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ABSTRACT: The fetal brain disruption sequence (FBDS), a rare cause of extreme microcephaly, is described in a patient and compared with 19 previously reported cases. Clinical findings present in almost all patients included: severe microcephaly (average occipitofrontal circumference -5.8 SD), overlapping sutures, prominent occipital bone, scalp rugae with normal hair patterning and marked neurological impairment. Early death occurred in 7/20 cases. The FBDS was sporadic in 17 out of 19 reported cases supporting a low recurrence risk for genetic counselling purposes. A group of related observations in cases were thromboembolic phenomenon following death of the co-twin, vascular and/or haematological involvement by prenatal cytomegalovirus infection, prenatal cocaine exposure, direct vascular fetal trauma (cordocentesis) and fetal vascular changes after a maternal car accident causing intracranial bleeding and brain damage. Normal scalp hair pattern in all cases and the second or third trimester location of the disruptive event in two cases suggest that in the FBDS, brain growth is normal throughout the first 18 weeks of gestation at least. Conclusion: pathogenic factors suggest that different forms of vascular injury to the fetal brain (emboli, haemorrhage, vasoconstriction, disseminated intravascular coagulation) can produce partial brain destruction, diminished intracranial pression and skull collapse in the fetal brain disruption sequence.
European Journal of Pediatrics 10/2001; 160(11):664-667. · 1.88 Impact Factor
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ABSTRACT: A holoprosencephaly, hypertelorism, and ectrodactyly syndrome (HHES) was described in three previous cases in whom chromosomes were apparently normal. We report on a 3-year-old boy with HHES and a de novo apparently balanced t(2;4)(q14.2;q35) confirmed by fluorescent in situ hybridization. He had severe growth and mental retardation, lobar holoprosencephaly, hypertelorism, microphthalmos, and iris, choroid, and retina colobomata. Less-severe facial involvement correlates with the semilobar type of holoprosencephaly; limb defects consisted of foot ectrodactyly and syndactyly. All previous HHES cases were sporadic and of unknown cause. A cryptic imbalance secondary to the translocation (2;4) in our patient may explain the phenotype. Am. J. Med. Genet. 90:423–426, 2000 © 2000 Wiley-Liss, Inc.
American Journal of Medical Genetics 02/2000; 90(5):423 - 426.
