ELSEVIER Mutation Research 352 (1996) 151

Fundamental and Molecular Mechanisms of Mutagenesis

Series: Current Issues in Mutagenesis and Carcinogenesis

Introduction to Current Issues Nos. 67-73

Human germ cell mutagens

Although we are aware of N 50 situations in which humans have succumbed to chemically in- duced cancer, we have no such examples of the chemical induction of germ cell mutations in hu- mans. This is due to a combination of factors, includ- ing the protective biological environment of germ cells, the absence of appropriate mutation epidemiol- ogy, and the immense size of the potential target for mutation induction. Thus, theoretically, all genes are potentially open to mutation, leading to dilution of any chemically induced mutations over the whole genome, with no single phenotype to monitor exclu- sively. The chemical induction of mutations in hu- man germ cells is therefore a legitimate toxicological concern, but one for which we have neither prece- dents nor practical means of assessment.

Prediction of the potential of a chemical to mutate human germ cells is further complicated by the available rodent germ cell mutation assays being rather cumbersome and expensive to conduct. Recent technical advances may lead to the development of more practical and more sensitive assays, but a

present expedient is to consider whether the avail- able rodent somatic cell mutation assays, such as the bone marrow cytogentic assays, will encompass po- tential germ cell mutagens. If this is so, then rodent germ cell mutagens will form a subset of rodent somatic cell mutagens/genotoxic carcinogens - agents already subject to regulation. There are those who legitimately question this simple paradigm, see- ing it as a means to down-play the potential germ cell mutagen problem. Equally, it is legitimate to use existing experimental data to evaluate the strength of the paradigm. Many such evaluations have been reported, as discussed in several of the following Current Issues. The latter were written independent of each other, but have been co-published in order to bring their related themes together. As ever, it is hoped that these Current Issues will trigger further discussion in this section of Mutation Research. Articles are published as received, within the normal limits of propriety.

John Ashby Zeneca CTL

0027.5107/96/$15.00 0 1996 Elsevier Science B.V. All rights reserved

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