Enhancement and inhibition of the induction by 7,12-dimethylbenz(a)anthracene of mammary tumours in female Sprague-Dawley rats

Abstract

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Link between Carcinogenicity and Hepatic Metabolism of 7,12-Dimethylbenz(α)anthracene

“…The enzyme system can be enhanced in the rat liver by the administration of various inducers [17,25,28,29,32] thus producing increased amounts of metabolites as well as further derivatives. However, in further publications the involvement of DMBA hydroxylation in mammary tumor induction has been indicated and contradicted [2,6,16,32].…”

“…The enzyme system can be enhanced in the rat liver by the administration of various inducers [17,25,28,29,32] thus producing increased amounts of metabolites as well as further derivatives. However, in further publications the involvement of DMBA hydroxylation in mammary tumor induction has been indicated and contradicted [2,6,16,32]. The com parison of DMBA and various immediate metabolites showed that both DMBA and 7-HOM-12MBA caused mammary cancer, although a shorter period was required for the induction of sarcomas by DMBA than its meta bolite; 12-HOM-7MBA, or 7,12-diHOMBA were inactive [2,16,33], Never theless it has been suggested that the carcinogenic activity of DMBA could be attributed to the formation of 7-HOM-12MBA and subsequent conver sion of this metabolite to an ether, yielding reactive ions at the site of action [16].…”

“…In contrast, a protective effect against this carcino gen by increased liver microsomal enzyme activity has also been reported [19,21,25,28,29,32]. It appears therefore, that conclusive evidence is still lack ing either to support or to rule out the possibility that the metabolic transfor mation of DMBA is a necessary step in its carcinogenic activity.…”

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

“…The capacity of lung cells to induce microsomal enzymes would seem to be advantageous in view of reports that prior administration of AHH-inducing agents to laboratory animals prevented tumorigenesis by BP (19) and induced AHH levels lead to rapid conversion to noncarcinogenic metabolites, then either inhibition or induction of the enzyme results in lower rates of tumor formation (14,(19)(20)(21).…”

Transformation of Hamster Cells In Vitro by Polycyclic Hydrocarbons without Cytotoxicity

“…Two experimental models have been used mainly for this purpose: the formation of mammary tumors in rats given oral doses of Me2BzA, and the determination of skin tumor formation in mouse skin. Induction of increased polycyclic-hydrocarbon hydroxylase activity by several different flavones and other compounds before the administration of Me2BzA inhibits breast tumor formation* (13); SKF525-A, an inhibitor of microsomal enzyme activity, leads to an increased incidence of tumor formation (14). The formation of skin tumors in mice has been inhibited by pretreatment of the skin with 5,6-BzFl as an inducing agent and BzP as a carcinogen (15); pretreatment with 7,S-BzFl, an inhibitor of the enzyme or a weakly inducing compound has been responsible for the inhibition of tumors when given 5 min before treatment with Me2BzA (9).…”