Detection of carcinogen-DNA adducts in human fetal tissues by the 32P-postlabeling procedure.

摘要

Tobacco smoke contains a number of genotoxic compounds that are metabolized to their biologically active forms that subsequently react with cellular DNA to form covalently bound carcinogen-DNA adducts. Several analytical procedures have been developed to detect these adducts in human tissues. Using the nuclease P1-enhanced 32P-postlabeling procedure for bulky adducts, we have detected at least 24 adducts in DNA isolated from placenta and umbilical cord DNA. Adducts were detected in both smokers and nonsmokers, but the relative adduct level (RAL) was significantly higher in smokers (42.8, 8 cases) than in nonsmokers (19.7, 11 cases). The origin of the adducts in nonsmokers remains unknown. The adduct levels in artery DNA were significantly lower than in the vein and the placenta, and a paired nonparametric analysis showed a significant association between the adduct levels in the three tissues. Our results show a maternal transfer of carcinogens present in cigarette smoke to fetal tissues and show that the tissues can metabolize the carcinogens to their DNA binding metabolites. The presence of adducts in fetal tissues may be indicative of genomic damage and may predispose the individual for the development of a serious disease later in life.