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.

The role of aryl hydrocarbon hydroxylase in 7,12-dimethylbenz(a)- anthracene skin tumorigenesis, on the mechanism of 7,8-benzoflavone inhibition of tumorigenesis.

Abstract: Summary Aryl hydrocarbon hydroxylase of mouse skin is inducible by benz(a)anthracene or 7,12-dimethylbenz(a)anthracene (DMBA) and is inhibited by 7,8-benzoflavone. 7,8-Benzoflavone inhibits the formation of covalently bound complexes of DMBA with DNA, RNA, and protein and also inhibits tumor formation caused either by a single application of DMBA, followed by croton oil treatment, or by the repeated application of DMBA. These results indicate that DMBA requires metabolic activation by aryl hydrocarbon hydroxylase for its carcinogenic activity. The inhibitory effect of 7,8-benzoflavone is limited to its application within 12 hr of administration of the DMBA, suggesting that the metabolic activation of DMBA is completed within 12 hr. The level of aryl hydrocarbon hydroxylase and DMBA tumorigenesis varies markedly in different mouse strains, indicating either that there are genetic differences in the profile of DMBA metabolite formation or that metabolic activation is necessary but not sufficient for DMBA tumorigenesis.

Effects of dietary perilla oil, soybean oil and safflower oil on 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis in female SD rats

Abstract: The effects of diet supplemented with perilla oil, which contains a large amount of n-3 alpha-linolenic acid, and n-6 linoleic acid rich soybean and safflower oil supplemented diets on 7,12-dimethylbenz[a]anthracene (DMBA)- and 1,2-dimethylhydrazine (DMH)-induced mammary gland and colon carcinogenesis were investigated in female SD rats. Groups of 23 or 24, 5 week old animals were first given three s.c. injections of 40 mg/kg body wt DMH followed by a single intragastric administration of 50 mg/kg body wt DMBA within 2 weeks of the commencement. Starting 1 week after the DMBA treatment, they were administered pellet diet containing 10% perilla oil, soybean oil or safflower oil for the succeeding 33 weeks. Histological examination revealed that the resultant numbers of mammary tumors per rat were significantly lower in rats given perilla oil diet (4.4 +/- 2.5) than in the soybean oil diet group (6.5 +/- 3.9). Furthermore, colon tumor incidence was significantly lower in animals receiving the perilla oil supplement (18.2%) than in those given safflower oil diet (47.4%), and the numbers of colon tumors per rat tended to be lowest in rats administered perilla oil. Also the incidence of nephroblastomas in rats receiving perilla oil diet (0%) was significantly lower than that for the soybean oil diet group (23.8%). The results thus indicate that the alpha-linolenic acid (n-3)-rich perilla oil diet inhibits development of mammary gland, colon and kidney tumors as compared to linoleic acid (n-6)-rich safflower or soybean oil diet.

Studies of Prostaglandins in Rat Mammary Tumors Induced by 7,12-Dimethylbenz(a)anthracene

Abstract: Studies are reported on the detection and synthesis of prostaglandins in the tissues of normal mammary glands and in mammary tumors induced by i.v. injection of 7,12-dimethylbenz(a)anthracene into female Sprague-Dawley rats. Thin-layer chromatography, using silicic acid and argentation adsorption techniques, indicated that prostaglandin E2 was the major prostaglandin of both tumorous and normal mammary gland tissue. The prostaglandin E concentration, determined by radioimmunoassay, was greater in the tissues of the mammary tumors than in the mammary glands of the normal control animals. Use of labeled substrates showed that prostaglandins were also synthesized in mammary gland tumors, and the synthetic activity appeared to be greater in the aberrant tissue than in the tissue of normal mammary glands.

Somatostatin Analogue Octreotide Enhances the Antineoplastic Effects of Tamoxifen and Ovariectomy on 7,12-Dimethylbenz(a)anthracene-induced Rat Mammary Carcinomas

Abstract: The efficacy of tamoxifen and ovariectomy in the management of breast cancer is limited by the resistance of many neoplasms to these endocrine therapies and by the fact that initially responding tumors often escape from control during long-term treatment. We evaluated the effect of coadministration of the somatostatin analogue octreotide, which has single agent activity in several in vivo and in vitro breast cancer models, on the antineoplastic actions of tamoxifen and ovariectomy on 7,12-dimethylbenz( a )anthracene-induced mammary tumors. Rats received tamoxifen (0.5 mg/kg twice weekly s.c.), octreotide (10 µg/kg/h for 6 weeks by osmotic minipump), or the combination 7 weeks following 7,12-dimethylbenz( a )anthracene administration. The number of tumors per animal and the sum of the volumes of palpable tumors per animal were significantly less in the combination treatment than in the others. In ovariectomized rats the marked regression of established tumors in the initial 4 weeks after ovariectomy was frequently followed by tumor regrowth. However, continuous infusion of octreotide (50 µg/kg/h for 6 weeks postovariectomy) significantly ( P < 0.01) suppressed this regrowth. Our data suggest that octreotide enhances the antitumor effects of tamoxifen or ovariectomy in the 7,12-dimethylbenz( a )anthracene mammary cancer model.