Time-dependent mutagenesis and cancer: a new role for antimutagenesis in cancer prevention?

Most attempts to identify potential antimutagens (and/or presumptive anticarcinogens) involve testing individual compounds or mixtures in tandem combinations with specific physical or chemical mutagens and measuring the sought-after reductions in mutation numbers in one or more experimental organisms. Relatively few investigators appear to have set out to identify antimutagens which are efficacious in reducing spontaneous mutation yields (possibly because of the poor mutation yields which tend to be available for downward manipulation in spontaneous mutation assays). The net effect is that we currently know very little about what may well prove to be one of the most interesting and exciting areas of antimutagenesis and anticarcinogenesis research in the future. This paper is primarily concerned with the main features of several interrelated (and often overlapping) pathways which are likely to be involved in the generation of newly-mutant sequences in cellular organisms in the absence of a deliberately-added mutagen. Attempts will be made to highlight some of the cellular processes which may have to be blocked in subtle (or perhaps even unsubtle) ways if we are to achieve our somewhat ambitious goal of discovering antimutagenic anticarcinogens which are both usable and useful in delaying the onset of primarily age-dependent mammalian cancers whose origins may well owe a great deal more to spontaneous mutations than they do to environmentally-provoked ones. (C) 1998 Elsevier Science B.V. All rights reserved.