Carcinogen activation, inhibition

Recent structure-activity studies of 1-alkylbenzo[a]pyrenes also suggest that DNA intercalation of benzo[a]pyrene (BP) metabolites plays a role in the mechanism of BP carcinogenesis (38). The addition of bulky alkyl groups at the 1-position of BP, which inhibit DNA intercalation of 1-alkyl-BP metabolites (19), causes a reduction in carcinogenic activity. 

In 1970, Rice et al. studied a diverse range of 3-substituted 1,2,3,4-tetrahydrocarba-zole derivatives in a preliminary pharmacological screening for general stimulation, depression, and autonomic activity, and found that 3-carboethoxy-9-(3-dimethyl-aminopropyl)-l,2,3,4-tetrahydrocarbazole (461) exhibited growth inhibition at a concentration of 1 gg/mL in mammary carcinoma tissue (400). These studies were based on the carcinogenic activity observed for the bis-angular bis-benzocarbazoles reported by Buu-Hoi et al. (401). 

Figure 15.2 Inhibition of carcinogen activation and induction of phase II detoxification enzymes by resveratrol.

Mutagenesis induced in Salmonella typhimurium by 2-fluorenamine and other chemical carcinogens was inhibited by low levels of retinol and other retinoids when carcinogen activation was carried out by rat liver microsomes. In contrast, low levels of retinoids enhanced mutagenesis when carcinogen activation was mediated by whole liver homogenates. There was no effect of the provitamin 3-carotene in this test system. 

High levels of retinol or retinyl acetate inhibit mutagenicity induced by aromatic amines in a Salmonella/mammalian microsome assay when carcinogen activation is carried out by S9 or purified microsomes ... 

The biochemical mechanisms responsible for the cancer-preventive effects of green tea have not been clearly defined. Laboratory studies have shown that green tea possesses antioxidant and free radical scavenger activities, inhibits cell proliferation," induces apoptosis, modulates carcinogen-metabolizing enzymes, " - and suppresses inflammatory responses, - all of which could contribute to the observed preventive effects. 

Anticarcinogens that either directly antagonize carcinogens, or more likely prevent their activation, are also present in many foods naturally or are added to them. Included in this list of good guys are vitamins A, E, and C, some Bs, chlorophyll, carotene, butylated hydroxytoluene (BHT), and anisole (BHA). Many of these substances are effective antioxidants that presumably may inhibit oxidative carcinogenic activation. Vitamin C is also a potent inhibitor of nitrosamine formation. 

Soc. 1958, 222 Tanenbaum, Bassett, J. Biol Chem. 234, 1861 (1959). Has carcinogenic activity attributable to a.P-unsaturation together with an external conjugated double bond attached to 4 position of the y -lactone ring Dickens, Brit. Med Bull 20, 96 (1964). Review amd evaluation of studies of carcinogenic action in laboratory animals IARC Monographs 10,205-210 (1976). Also inhibits uptake of K+ ions in erythrocytes Kahn, J. Pharmacol Exp. Then 121, 234 (1957). Toxicity R. Kinostta, T. Shikata, "On Toxic... 

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