Preconception exposure to mutagens: medical and other exposures to radiation and chemicals

Abstract

Contrary to intuition, no environmental exposure has been proved to cause human germ line mutations that manifest as heritable disease in the offspring, not among the children born to survivors of the American atomic bombs in Japan nor in survivors of cancer in childhood, adolescence, or young adulthood who receive intensive chemotherapy, radiotherapy, or both. Even the smallest of recent case series had sufficient statistical power to exclude, with the usual assumptions, an increase as small as 20 % over baseline rates. One positive epidemiologic study of a localized epidemic of Down syndrome in Hungary found an association with periconceptual exposure to a pesticide used in fish farming, trichlorfon. Current population and occupational guidelines to protect against genetic effects of ionizing radiation should continue, with the understanding they are based on extrapolations from mouse experiments and mostly on males. Presently, pre-conceptual counseling for possible germ cell mutation due to the environment can be very reassuring, at least based on, in a sense, the worst-case exposures of cancer survivors. Prudence demands further study. Future work will address the issue with total genomic sequencing and epigenomic analysis.

Fig. 1

Filling the void in understanding human germ cell mutagenesis (adapted from Sobels 1993)