7,12-Dimethylbenz[a]anthracene

About: 7,12-Dimethylbenz[a]anthracene is a research topic. Over the lifetime, 1717 publications have been published within this topic receiving 40892 citations.

Susceptibility of chromosomes from patients with Down's syndrome to 7,12‐dimethylbenz(a) anthracene‐induced aberrations in vitro

Abstract: The susceptibility of chromosomes from seven patients with Down's syndrome to damage in vitro by 7,12-dimethylbenz (a)anthracene (DMBA) was significantly greater than that of the chromosomes from ten healthy donors. Chromatid gaps or breaks comprised the vast majority of aberrations produced in the chromosomes of both groups. Small numbers of isochromatid exchanges and dicentric chromosomes were also observed. The lymphocytes of patients with Down's syndrome were not deficient in their ability to repair DNA damage induced by ultraviolet light or 4-nitro-quinoline-N-oxide and, at the doses used to produce chromosomal aberrations, DMBA did not significantly inhibit either replicative DNA synthesis or the repair of damage induced by ultraviolet light or 4-nitroquinoline-N-oxide in normal lymphocytes or in those from patients with Down's syndrome. DMBA did not stimulate unscheduled DNA synthesis in the lymphoeytes from patients with Down's syndrome or from normal controls.

Oxidation of the trans-3,4-Dihydrodiol Metabolites of the Potent Carcinogen 7,12-Dimethylbenz(a)anthracene and Other Benz(a)anthracene Derivatives by 3α-Hydroxysteroid-dihydrodiol Dehydrogenase: Effects of Methyl Substitution on Velocity and Stereochemical Course of trans-Dihydrodiol Oxidation

Abstract: The homogeneous 3α-hydroxysteroid-dihydrodiol dehydrogenase of rat liver cytosol catalyzes the NADP-dependent oxidation of a wide variety of polycyclic aromatic trans -dihydrodiols and has been implicated in their detoxification (T. E. Smithgall, R. G. Harvey, and T. M. Penning, J. Biol. Chem., 261: 6184–6191, 1986). This study examined the influence of methyl groups on the velocity and stereochemical course of enzymatic benz( a )anthracene (BA) trans -dihydrodiol oxidation. The racemic trans -3,4-dihydrodiols of BA and 7-methylbenz( a )anthracene (7-MBA) were completely consumed by the purified dehydrogenase, indicating that both stereoisomers are substrates. However, 50% of the (±)- trans -3,4-dihydrodiols of 12-methylbenz( a )anthracene (12-MBA) and 7,12-dimethylbenz( a )-anthracene (DMBA) were oxidized, suggesting that only one stereoisomer is utilized in each case. At low substrate concentrations, enzymatic oxidation of the trans -3,4-dihydrodiois of BA, 12-MBA, and DMBA followed simple first-order kinetics. By contrast, oxidation of the 3,4-dihydrodiol of 7-MBA was of higher order, due to differences in the rate of oxidation of each stereoisomer. Rate constants estimated for each reaction indicate that the non-bay-region methyl group at position 7 has a greater enhancing effect on the rate of oxidation than the bay-region methyl group at position 12 (10- versus 4-fold, respectively). The 3,4-dihydrodiol of DMBA, which possesses both non-bay- and bay-region methyl groups, is oxidized more than 30 times faster than the unmethylated parent hydrocarbon. The absolute stereochemistry of the preferentially oxidized dihydrodiols was assigned by circular dichroism spectrometry. For the 3,4-dihydrodiols of DMBA and 12-MBA, the stereoisomer oxidized has the 3 S ,4 S configuration. A large negative Cotton effect was observed in the circular dichroism spectrum of the 7-MBA 3,4-dihydrodiol which remained at the end of the rapid phase of oxidation of this racemic substrate, indicating that the dehydrogenase displays partial stereochemical preference for the 3 S ,4 S enantiomer. These results suggest that methylation of BA at C-7 greatly enhances the oxidation of the 3 S ,4 S -dihydrodiol, while the presence of a bay-region methyl group at C-12 completely blocks the oxidation of the 3 R ,4 R -stereoisomer. Rapid, stereoselective oxidation of methylated polycyclic aromatic trans -dihydrodiols by this route in vivo may significantly influence their carcinogenicity.