Individual susceptibility to induced chromosome damage and its implications for detecting genotoxic exposures in human populations.
In a previous study, we observed a bimodal distribution of sensitivity to sister chromatid exchange (SCE) induction by diepoxybutane (DEB) in lymphocytes from healthy individuals. Twenty-four % of the participants had increased sensitivity to in vitro induction of SCEs and chromosomal aberrations. These same participants also had significantly higher frequencies of uninduced or baseline SCE frequencies. In the present study, we measured baseline and DEB-induced SCE frequencies in 55 healthy female volunteers. Eleven of 55 [20%] women were relatively sensitive to DEB induction of SCEs. Baseline SCE frequencies in these sensitive individuals [10.4 +/- 0.7 (SD) SCEs/cell] were significantly higher [P less than 0.001; Student's t test] than baseline SCE frequencies in the remaining 44 individuals [8.0 +/- 0.9 SCEs/cell]. Similar increases in SCEs were observed when the analysis was restricted to the upper 10% of the SCE distribution (high frequency SCE analysis). The phenotype of DEB sensitivity accounted for 58% of the variation among individual SCE scores. Given the population frequency of this sensitivity to SCE induction and the high proportion of variance in SCEs for which it accounts, failure to account for this factor could seriously distort conclusions about SCE measures associated with other environmental exposures. The most likely result of such unexplained variability (type II error) would be bias toward the null hypothesis. Also, the likelihood that individual variations contribute to false positive results is expected to be greatest in studies that compare small numbers of exposed and nonexposed individuals. To summarize, these results confirm our earlier study and show that increased baseline SCE frequencies can be indicative of increased sensitivity to certain classes of mutagenic carcinogens. Identification of DEB-sensitive persons could be used to increase the sensitivity of SCE analysis in monitoring studies to detect exposure to genotoxins.
Wiencke
J K
JK
Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco 94143-0560.
Wrensch
M R
MR
Miike
R
R
Petrakis
N L
NL
D000328:Adult; D000704:Analysis of Variance; D002478:Cells, Cultured; D004361:Drug Tolerance; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009153:Mutagens / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects
D004852:Epoxy Compounds; D009153:Mutagens; C007366:diepoxybutane