Background DNA damage for endogenous and unavoidable exogenous carcinogens: a basis for spontaneous cancer incidence?

It is undisputed today that DNA is constantly being damaged in the absence of any exposure to genotoxic carcinogens by a specific treatment or a particular habit. Damaging processes include endogenous and unavoidable exogenous sources. The list comprises chemical DNA instability (eg., depurination), spontaneous errors during DNA replication and repair, endogenous reactive chemicals (aldehydes, S-andenosylmethionine), numerous reactive oxygen species and products generated in consequence (e.g., lipid peroxides). Exogenous sources are ionizing and UV radiation, naturally occurring radioisotopes, and numerous genotoxic chemicals present in diet and air, both naturally or as contaminants. DNA repair and DNA replicative synthesis result in a constant reduction of the level of damage, but a certain steady-state level is measurable as a background at all times. The quantitative relationship between the background DNA damage and the spontaneous rates of mutation and cancer remains largely unknown. The quantitative relationship between the background DNA damange and the spontaneous rates of mutationa and caner remains largley unknown. In order to establish better correlations, more data have to be accumulated. This includes (i) measuring artefact-free levels of background DNA damage, (ii) investigating the mutagenic potency of the various lesions, (iii) including types of DNA damage other than adducts, and (iv) answer the question of organ-specific and cell type-specific +requirements for the primary DNA damage to be expressed as heritable genetic changes. The manuscripts put together for this Special Issue of Mutation Research describe the state of the art for these aspects.