Cigarette sidestream smoke delays nucleotide excision repair: inhibited accumulation of repair proteins at DNA lesions

Cigarette sidestream smoke delayed nucleotide excision repair in vivo and in vitro. This delay was attributed to the inhibited accumulation of DNA repair molecules at damaged sites, which was mainly caused by aldehydes in cigarette sidestream smoke. Cigarette sidestream smoke (CSS) contains many carcinogens that induce DNA damage. DNA damage plays an important role in the initiation of cancer and several diseases, and repair is the major defense mechanism; however, the relationship between CSS and the repair of DNA damage remains unclear. We herein investigated whether CSS influences nucleotide excision repair (NER) in vivo and in vitro. HR-1 hairless mouse skin treated with CSS was exposed to UVB, as a result of which pyrimidine dimers (cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs)) were formed and repaired via the NER pathway. The immunohistochemical staining of CPDs revealed that their repair was delayed by the CSS treatment. This delay in NER and the underlying mechanisms were examined in the human skin cell lines, HaCaT and HSC-1. Dot-blot assays, enzyme-linked immunosorbent assay and local ultraviolet irradiation assays demonstrated that CSS delayed the repair of CPDs and 6-4PPs. The recruitment of the repair molecules, TFIIH, XPA and XPG to pyrimidine dimers was markedly inhibited by CSS. Semicarbazide, which reacts with aldehydes, recovered the CSS-induced inhibition of NER, and formaldehyde exerted similar inhibitory effects to those of CSS. These results suggest that aldehydes in CSS interfere with the recruitment of NER molecules to damaged sites, leading to a delay in the repair of pyrimidine dimers.