The Effects of GSTM1 and GSTT1 Polymorphisms on Micronucleus Frequencies in Human Lymphocytes In vivo

Abstract

The influence of genetic polymorphisms in GSTM1 and GSTT1 genes on micronucleus frequencies in human peripheral blood lymphocytes was assessed through a pooled analysis of data from seven laboratories that did biomonitoring studies using the in vivo cytokinesis-block micronucleus assay. A total of 301 nonoccupationally exposed individuals (207 males and 94 females) and 343 workers (237 males and 106 females) occupationally exposed to known or suspected genotoxic substances were analyzed by Poisson regression. The results of the pooled analysis indicate that the GSTT1 null subjects had lower micronucleus frequencies than their positive counterparts in the total population (frequency ratio, 0.55; 95% confidence interval, 0.33-0.89). The protective effect of this genotype is reversed with increasing age, with a frequency ratio of 1.33 (95% confidence interval, 1.06-1.68) in subjects aged 60 years. A significant overall increase in micronucleus frequency with age and gender (P < 0.001 and P = 0.024, respectively) was observed, females having higher micronucleus frequencies than males, when occupationally exposed (P = 0.002). Nonoccupationally exposed smokers had lower micronucleus frequencies than nonsmokers (P = 0.001), whereas no significant difference in micronucleus level was observed between smokers and nonsmokers in the occupationally exposed group (P = 0.79). This study confirms that pooled analyses, by increasing the statistical power, are adequate for assessing the involvement of genetic variants on genome stability and for resolving discrepancies among individual studies. (Cancer Epidemiol Biomarkers Prev 2006;15(5):1038 -42)

Effects of age on the frequency of micronuclei and degenerative nuclear abnormalities

“…During the aging process, the enzymes involved in DNA repair become less and less common, which increases the susceptibility of cells to genotoxic agents. 31,32 Kirsch-Volders et al 33 suggested that flaws in the cellular defense systems that protect against DNA damage, as well as the reduced efficiency of DNA repair, can lead to an accumulation of mutations. These mutations, either in isolation or in combination with other age-related alterations, can contribute to aging and the development of age-related illnesses.…”

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

“…Frequency ratio (FR), its confidence interval (CI), and the corresponding P values were reported. For categorical variables, the FR indicates the proportional increase of the micronucleus frequency in the study group; for example, a FR of 1.21 for females versus males means a 21% increase of micronucleus frequency in females (35). In order not to ignore important risk factors in such an exploratory multivariate analysis, the test level was relaxed to 0.10 (as the default test level of stepwise linear regression model in SAS package is 0.15, not the usual 0.05).…”

Genotoxicity Biomarkers: Application in Histopathology Laboratories

“…Cytogenetically, ageing is associated with a number of gross cellular changes, including altered size and morphology, genomic instability and changes in expression and proliferation (Bolognesi et al, 1999;Zietkiewicz et al, 2009). It has been shown that a higher MN frequency is directly associated with decreased efficiency of DNA repair and increased genome instability (Kirsch-Volders et al, 2006;Orsière et al, 2006). The data has shown a significant increase of MN in lymphocytes in the exposed group.…”