Biomonitoring for genotoxic effects has a low sensitivity in terms of cancer risks associated with lifelong exposures starting in utero.
Cancer risk is probably function of the accumulation of mutations in stem cells. These stem cells divide probably about 10 times less frequently than peripheral cell populations. In the case of exposure during adulthood, the peripheral cell populations dividing at the time of exposure will present an increased mutant frequency that can be detected by a biomonitoring test. Stem cells will have divided only a few times during a limited time period in adulthood. The risk of cancer, being in essence a function of the mutant frequency of stem cells and increasing exponentially with it, will only be moderately increased, and the ratio between the results of genotoxicity tests (performed during or shortly after exposure) and the increase in cancer risk will be sufficient to be useful. In the case of a lifelong exposure, starting in utero, the ratio between induced mutant frequency (and cancer risk) in stem cells and induced mutant frequency in peripheral cells will be larger than for an exposure during a limited time period in adulthood. As a consequence, for the same (detectable) increase in mutant frequency in peripheral cells, a larger increase in cancer risk is to be expected in the case of a lifelong exposure starting in utero.
van Larebeke
N
N
Study Centre for Carcinogenesis and Primary Prevention of Cancer, Ghent University, Universitary Hospital 3K3, De Pintelaan 185, B 9000 Gent, Oost Vlaanderen, Belgium. nicolas.vanlarebeke@ugent.be
D000328:Adult; D004781:Environmental Exposure; D004784:Environmental Monitoring; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000502:physiology*; D009369:Neoplasms / Q000453:epidemiology*; D016273:Occupational Exposure; D011247:Pregnancy; D018570:Risk Assessment; D013234:Stem Cells / Q000187:drug effects
D009153:Mutagens