Three measures of mutagen sensitivity in a cancer-free population.
Different individuals appear to respond differently to the same carcinogen, and different mutagens act differently on cells. We conducted mutagen sensitivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to determine the relationships among these assays. Our results showed that the mean breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age, sex, smoking status, and family history of cancer were not correlated with any of these mutagen sensitivities. Also, there was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th percentile of b/c was used as a cutoff point in each assay, only one individual (1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of three mutagens. Our study suggests that these three mutagens may involve different DNA damage and repair pathways. The lack of correlation between the assay results may indicate the necessity of using a battery of mutagen sensitivity tests to refine our ability to identify a subpopulation at high cancer risk.
Gu
J
J
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Bondy
M L
ML
Sigurdson
A
A
Spitz
M R
MR
Hsu
T C
TC
Wu
X
X
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000633:toxicity; D004249:DNA Damage; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000209:etiology*
D009153:Mutagens; D001761:Bleomycin; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D015112:4-Nitroquinoline-1-oxide