The contribution of exogenous and endogenous mutagens to in vivo mutations

There is abundant evidence of the potential for exogenous agents to cause cancer but the proportion of human cancers attributable to defined external agents is uncertain. With rare exceptions it is difficult to demonstrate a role for exogenous agents in increasing mutation above background rates. There are many sources of endogenous mutation including physico-chemical processes, free radicals and enzymatic processes controlling DNA damage and repair. Evidence for the role of diet and genetic factors as major determinants of endogenous mutagenesis is reviewed with reference to the spontaneous spectrum of mutations in human cells and the quantitative measurement of mutation frequency in dietary restriction and the senescence-accelerated mouse.