Tritium-labeled 3-methyldibenzo(c,g)carbazole and 5,9-dimethyldibenzo(c,g)-carbazole, 2 organ-specific hepatocarcinogens in mice, were given intraperitoneally to partially hepatectomized animals at various times during the first cell division cycle following surgery. The former compound, more potent and cytotoxic, gave more striking results showing that the maximum number of adducts per unit weight of DNA in liver were formed when the carcinogen was given at the beginning of the S phase, which is evidence for the role of DNA replication in the initiation step of carcinogenesis. Elimination of these adducts led after several days to a residual number of lesions which was of the same order whatever the time of carcinogen administration. In the case of 5,9-dimethyldibenzo-carbazole there were fewer adducts formed after hepatectomy and their removal was much slower.

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http://dx.doi.org/10.1016/0248-4900(90)90292-bDOI Listing

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