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.

Metabolism and toxicity of xenobiotics in the adrenal cortex, with particular reference to 7,12-dimethylbenz(a)anthracene.

Abstract: The adrenal cortex contains high amounts of detoxifying enzymes, as well as generators and protectors of reactive oxygen species. The high content of cytochrome P-450 enzymes in the adrenal cortex together with its remarkable tendency to accumulate hydrophobic substances probably contributes to the extraordinary vulnerability of the gland to a number of xenobiotics. The best studied adrenocorticolytic compounds are the potent carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) and its liver metabolite 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA). Adrenocorticolysis generated by these agents in vivo as well as in vitro demonstrates high regioselective requirements and is strongly influenced by the presence of ACTH, steroids, cytochrome P-450 inhibitors and antioxidants. Furthermore, 7-OHM-12-MBA has been demonstrated to uniquely generate selective and massive oxidation of mitochondrial glutathione in cultured rat adrenal cells. The DMBA-induced adrenocorticolysis is thoroughly discussed in this review with particular emphasis on the metabolism of DMBA and the influence of various effectors. A working hypothesis involving a possible peroxidative mechanism is also presented.

Lack of promotion of 7,12-dimethylbenz[a]anthracene-initiated mouse skin carcinogenesis by 1.5 GHz electromagnetic near fields.

Abstract: The effects of 1.5 GHz electromagnetic near fields of time division multiple access (TDMA) signal for the Personal Digital Cellular, Japanese cellular telephone standard (PDC) used for cellular phones, on mouse skin carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) were examined. Ten-week-old ICR female mice were treated with a single application of DMBA on shaved dorsal skin by painting at a concentration of 100 microg/100 microl acetone per mouse. One week later, mice were divided into four groups, receiving electromagnetic near fields exposure (DMBA-EMF), sham-exposure (DMBA-Sham), 12-O-tetradecanoylphorbol-13-acetate (TPA, 4 microg /200 microl acetone/mouse), as a positive control (DMBA-TPA), and no-treatment (DMBA-Control). EMF near fields exposure conditions were as follows: skin local peak specific absorption rate (SAR) 2.0 W/kg, whole body average SAR 0.084 W/kg (ratio of peak to average SAR is 24), 90 min a day, 5 days a week, for 19 weeks. At week 20, animals were killed and skin tumors were analyzed histopathologically. The incidences of skin tumors in DMBA-EMF, DMBA-Sham, DMBA-TPA and DMBA-Control groups were 0/48 (0%), 0/48 (0%), 29/30 (96.6%) and 1/30 (3.3%), respectively. Histopathologically, papilloma and squamous cell carcinoma (SCC) were observed in the DMBA-TPA group and only papilloma observed in the DMBA-Control group. The incidences of squamous cell papillomas and squamous cell carcinomas in DMBA-TPA and DMBA-Control groups were 29/30 (96.6%) and 1/30 (3.3%), respectively, numbers of tumors per mouse (tumor multiplicity) being 18.8 +/- 13.4 and 0.1 +/- 0.5. These data clearly demonstrated that near fields exposure to 1.5 GHz EMF, used for cellular phones, does not exert any enhancing effect on skin tumorigenesis initiated by DMBA.

Inhibition of 7,12-dimethylbenz[a]anthracene-induced lipid peroxidation and mammary tumor development in rats by vitamin E in conjunction with selenium.

Abstract: The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12-dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague-Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA-induced mammary carcinogenesis.

Embryopathic effects of 7,12-dimethylbenz(a)anthracene and its hydroxymethyl derivatives in the Sprague-Dawley rat.

Abstract: 7, 12-Dimethylbenz(a)anthracene and one of its hydroxymethyl derivatives have been shown to cause a variety of foetal abnormalities, especially when administered on day 13 of pregnancy. It is suggested that derivatives of benz(a)anthracene must have active side chains situated at C-7 and C-12 for embryopathic activity.