International study of factors affecting human chromosome translocations.
ABSTRACT Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.
Article: Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population.[show abstract] [hide abstract]
ABSTRACT: To obtain a relationship between background chromosome translocation frequency and age with translocation frequency measured to a high statistical precision, and to identify the role of background ionizing radiation in the production of chromosome translocations in a control population. Lymphocytes from 35 healthy control individuals (15 females and 20 males) were scored, using fluorescence in situ hybridization, for the presence of chromosomal translocations. Translocation frequencies were measured to a high statistical precision (s.d. 25% or less for each individual). These control subjects were of varying ages, ranging from 0 (cord blood) to 98 years. In a total of 521,492 metaphases (203,754 genome equivalent cells) scored, an average of 5,822 genome equivalent cells per individual, 764 translocations were observed in the 35 individuals. The translocation frequencies ranged from 0 (for cord blood) to 0.0167 (for a 98 year old) translocations per cell. The average age and translocation frequency was 50 years and 0.004 translocations per cell, respectively. The best fit of the relationship between translocations and age was: Y=7x10(-4)+6.9x10(-6)A+1.35x10(-6)A2, which does not obey the linear relationship expected from chronic background radiation alone. The curvilinear relationship observed clearly shows that other endogenous and exogenous clastogens or clastogenic events, in addition to radiation, serve to generate chromosome translocations in control populations. The background translocation frequency in control individuals follows a curvilinear relationship with age. No significant variation was observed between individuals of the same age. Clastogenic processes of normal aging and physiological factors in additional to ionizing radiation play a major role in the production of chromosome translocations in a control population. Background radiation, however, appears to play a minor role in chromosome translocation production in control individuals living near sea level.International Journal of Radiation Biology 08/1999; 75(7):819-27. · 2.28 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Chromosome aberration frequencies in a group of new entrants and non-radiation workers from this establishment have been studied using both block-staining and G-banding techniques. Increased levels of chromosome exchanges were found in those with a previous history of occupational or medical exposure to potential clastogens and in smokers. The possibility of an age effect was suggested. The study emphasizes the problems encountered in obtaining suitable control levels for comparison with occupational studies of exposure to clastogens.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 01/1988; 182(6):303-8. · 2.85 Impact Factor
Article: Pharmacokinetics of a new oral antibacterial agent, ofloxacin, in dentistry and oral surgery.[show abstract] [hide abstract]
ABSTRACT: The new oral antibacterial agent, ofloxacin, was administered for prophylactic purposes to a group of 12 patients with dental and oral inflammatory processes requiring oral surgery. Drug concentrations in serum, saliva and gingival mucosa were assayed at different times after administration of the drug. Good serum, salivary and gingival mucosal tissue concentrations were achieved.International journal of clinical pharmacology, therapy, and toxicology 04/1988; 26(3):162-4.