Tsutomu Nakayama

Cigarette smoke induces DNA single-strand breaks in human cells

Epidemiological evidence suggests that smoking is a major cause of human lung cancer1,2. However, the mechanism by which cigarette smoke induces the cancer remains obscure, although in tobacco Carcinogenesis, promotion and/or co-carcinogenesis may have crucial roles. The epidemiological data show that if an individual stops smoking, the risk of his contracting lung cancer increases no further. Moreover, laboratory experiments show that cigarette smoke condensate (CSC) exhibits co-carcinogenic and promoting activities in tumour production and malignant transformation3–5. Clastogenic action is thought to be intimately involved in tumour promotion6–8, and it is therefore interesting that visible chromosome changes such as chromosome aberrations and sister chromatid exchanges are known to be caused by cigarette smoke9–11. However, there has been no previous direct demonstration that cigarette smoke can cause single-strand breaks (SSB) in DNA. Here we report that cigarette smoke induces considerable numbers of DNA SSB in cultured human cells, and that such strand breaks may be ascribed to active oxygen generated from cigarette smoke.

Activation of deoxycholic acid by the lipid peroxy radical and its covalent binding to nucleic acids.

Deoxycholic acid, a colon tumor promoter, was found to bind covalently to DNA and RNA in the presence of methyl linoleate hydroperoxide and ferrous ion. This binding was shown to occur specifically with guanine residues and its covalent nature was demonstrated by analysis of hydrolysates of nucleic acid adducts. These findings are discussed in connection with the increased risk of colon cancer associated with a high fat and meat diet.