Ultraviolet (UV) irradiation from the sun has been epidemiologically and mechanistically linked to skin cancer, a spectrum of diseases of rising incidence in many human populations. Both non-melanoma and melanoma skin cancers are associated with sunlight exposure. In this review, we discuss the UV wavelength-dependent formation of the major UV-induced DNA damage products, their repair and mutagenicity and their potential involvement in sunlight-associated skin cancers. We emphasize the major role played by the cyclobutane pyrimidine dimers (CPDs) in skin cancer mutations relative to that of (6–4) photoproducts and oxidative DNA damage. Collectively, the data implicate the CPD as the DNA lesion most strongly involved in human cancers induced by sunlight.

The fact that acrylamide, a proven rodent carcinogen, is present in significant quantities (up to several mg/kg of foodstuff) in a wide range of commonly consumed human foods is alarming. Attempts to determine a possible involvement of dietary acrylamide in human cancers have not been conclusive, however. To resolve the carcinogenicity of acrylamide to humans, the as yet unknown mechanism of action of acrylamide needs to be unraveled. The present review is a synopsis of research on the known and hypothetical modes of action of acrylamide of relevance for carcinogenesis. Both genotoxic and non-genotoxic modes of action of acrylamide are discussed with special emphasis on DNA adduct-targeted mutagenesis. Mechanistic data are presented from various experimental systems including in vitro experiments and in vivo rodent and human studies with special focus on mouse models. Human exposure data, including estimates of daily intake of dietary acrylamide in different populations and the corresponding cancer risk assessments are provided. The significant gaps in knowledge, which currently preclude a more definitive evaluation of human cancer risk due to exposure to dietary acrylamide, are highlighted. Future directions for research on acrylamide and cancer are outlined, and potential challenges are underscored.

Background: Acrylamide, a known rodent carcinogen, is found in the human diet. However, the mechanism by which acrylamide exerts its carcinogenic effects remains unclear. Methods: Normal human bronchial epithelial cells and Big Blue mouse embryonic fibroblasts that carry a λ phage cII transgene were treated in vitro with acrylamide, its primary epoxide metabolite glycidamide, or water (control) and then subjected to terminal transferase–dependent polymerase chain reaction to map the formation of DNA adducts within the human gene encoding p53 (TP53) and the cII transgene. The frequency and spectrum of glycidamide-induced mutations in cII were examined by using a λ phage–based mutation detection system and DNA sequence analysis, respectively. All statistical tests were two-sided. Results: Acrylamide and glycidamide formed DNA adducts at similar specific locations within TP53 and cII, and DNA adduct formation was more pronounced after glycidamide treatment than after acrylamide treatment at all doses tested. Acrylamide–DNA adduct formation was saturable, whereas the formation of most glycidamide–DNA adducts was dose-dependent. Glycidamide treatment dose-dependently increased the frequency of cII mutations relative to control treatment ( P <.001). Glycidamide was more mutagenic than acrylamide at any given dose. The spectrum of glycidamide-induced cII mutations was statistically significantly different from the spectrum of spontaneously occurring mutations in the control-treated cells ( P = .038). Compared with spontaneous mutations in control cells, cells treated with glycidamide or acrylamide had more A→G transitions and G→C transversions and glycidamide-treated cells had more G→T transversions ( P <.001). Conclusion: The mutagenicity of acrylamide in human and mouse cells is based on the capacity of its epoxide metabolite glycidamide to form DNA adducts.