The genotoxicity of 1-methylpyrene, 1,6-dimethylpyrene, 1-methylfluorene, 9-methylfluorene, and 1,9-dimethylfluorene was evaluated in the hepatocyte primary culture/DNA repair test, and the tumorigenic potency of these compounds was tested by bioassay in newborn mice. With the exception of 1-methylfluorene, all of these methylated polycyclic aromatic hydrocarbons are known mutagens in Salmonella typhimurium. Both 1-methylpyrene and 1,6-dimethylpyrene induced unscheduled DNA synthesis in rat hepatocytes. However, only 1-methylpyrene was tumorigenic when administered to newborn male mice. None of the methylated fluorenes assayed in the hepatocyte primary culture/DNA repair test induced unscheduled DNA synthesis. While 1,9-dimethylfluorene exhibited weak tumorigenic activity when administered by subcutaneous injection to newborn mice, 1-methylfluorene and 9-methylfluorene were inactive.
Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and enantiomeric 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes (BaP-7,8-diols) in mouse skin. Similar to enhancement of BaP carcinogenesis, repeated concurrent applications of catechol and (+/-)-BaP-7,8-diol to mouse skin strongly enhanced (+/-)-BaP-7,8-diol tumor multiplicity and tumor incidence, and decreased latency. Co-application of catechol with the racemic or either of the enantiomers of BaP-7,8-diol in a two-stage initiation--promotion protocol increased the tumor initiating activity of racemic BaP-7,8-diol, similar to that of BaP, by approximately 50%, but had no statistically significant effect on the tumor initiating activity of the (+)- or (-)-enantiomers in mouse skin. Thus, catechol is as potent a co-carcinogen with (+/-)-BaP-7,8-diol as it is with BaP. However, as tested here catechol is a weak co-initiator when applied with (+/-)-BaP-7,8-diol or BaP.
7-OHIQ is not genotoxic, for to be so classified it must be definitely positive in both the Ames and Williams tests; moreover, it is not carcinogenic, in marked contrast to IQ and NMU.
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