Different individuals appear to respond differently to the same carcinogen,
and different mutagens act differently on cells. We conducted mutagen sens
itivity assays by using three mutagens (bleomycin, a radiomimetic agent; 4-
nitroquinoline-1-oxide [4-NQO], an ultraviolet light mimetic agent; and ben
zo[a]pyrene diol epoxide [BPDE], a tobacco mutagen) in parallel in healthy
human subjects to determine the relationships among these assays. Our resul
ts 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 can
cer were not correlated with any of these mutagen sensitivities. Also, ther
e was no correlation between bleomycin and 4-NQO or 4-NQO and BPDE sensitiv
ity, but a weak correlation between bleomycin and BPDE was observed (correl
ation 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 sensit
ive to all three mutagens. Ten individuals (17.9%) were sensitive to two mu
tagens, 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 da
mage 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. (C)
Elsevier Science Inc., 1999. All rights reserved.