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.

Suppressive effect of sesamin against 7,12-dimethylbenz[a]-anthracene induced rat mammary carcinogenesis.

Abstract: The effects of dietary supplementation of sesamin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats were studied. Experimental diets containing 0.2% sesamin (an equiweight mixture of sesamin and episesamin) or 0.2% alpha-tocopheryl acetate were given to rats starting 1 week before intragastric administration of DMBA (10 mg/rat). Sesamin significantly (p less than 0.05) reduced the cumulative number of palpable mammary cancers by 36% at 12 weeks post-DMBA administration compared with animals on a control diet. Alpha-tocopheryl acetate inhibited both the incidence and the cumulative number of mammary tumors by 20% and 45%, respectively. Concentrations of lipid peroxides in plasma, liver and tumors were all decreased in both sesamin and alpha-tocopheryl acetate groups. The activity of peripheral blood mononuclear cells (PBMC) increased in rats fed sesamin (140 to 150% of the control and alpha-tocopheryl acetate groups). Fatty acid compositions of plasma, liver and tumor phosphatidylcholine showed a decreased tendency of the metabolism of linoleic acid to arachidonic acid and hence of the plasma concentration of prostaglandin E2 in the sesamin group. The inhibitory effect of sesamin on DMBA-induced mammary carcinogenesis may be ascribed, at least in part, to immunopotentiation and increased antioxidative activity.

Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice.

Abstract: We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti-tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2-stage carcinogenesis model. A single topical pretreatment to mouse skin (2 μmol) 24 hr before application of dimethylbenz[a]anthracene (0.2 μmol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post-initiation phase reduced the number of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol)-induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 μmol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase-1, glutathione S-transferase-P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome P450 1A1 or 1B1. Further, it diminished TPA-induced cyclooxygenase-2 protein expression and phosphorylation of extracellular signal-regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application-induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti-oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways. © 2004 Wiley-Liss, Inc.

Neoplasia in zebrafish (Danio rerio) treated with 7,12-dimethylbenz[a]anthracene by two exposure routes at different developmental stages.

Abstract: Using zebrafish, Danio rerio, initial pioneering work in the 1960s revealed carcinogen responsiveness of fish, yet very few subsequent tumorigenesis investigations have utilized this species. We exposed embryos (60 hours postfertilization) and fry (3 week posthatch) to 7,12-dimethylbenz[a]anthracene (DMBA) by immersion in aqueous solutions for 24 hours, at concentrations of 0-1 or 0-5 ppm (mg/L), respectively. Juvenile zebrafish 2 months posthatch were fed a diet containing 0-1,000 ppm DMBA for 4 months. Fish were sampled for histologic evaluation at 7-12 months after the onset of carcinogen treatment. Fry were most responsive to DMBA and showed the widest diversity of target tissues and histologic types of neoplasia, having several types of epithelial, mesenchymal, and neural neoplasia. The principal target tissues for carcinogenic response were liver following embryo or fry exposure, with gill and blood vessel the second and third most responsive tissues in fry. Intestine was the primary target and gill a secondary target in fish that received dietary DMBA as juveniles. These studies indicate that young zebrafish are most responsive to DMBA, showing a greater diversity of neoplasm types than rainbow trout. Thus, zebrafish are a valuable model system in which to study mechanistic aspects of the carcinogenesis process.

Impact of various sources of garlic and their constituents on 7,12-dimethylbenz[a]anthracene binding to mammary cell DNA.

Abstract: The present studies assessed the impact of various sources of garlic and their constituents (water- and ethanol-extracts and S-allylcysteine) on the in vivo binding of the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) to rat mammary cell DNA. The provision of dietary raw garlic powder (2%) or its water-extract (1.5%) reduced DMBA-DNA binding by 33 and 46% respectively. Dietary supplementation with a commercially available deodorized garlic powder (powder A) at 2 or 4% depressed the occurrence of adducts by 50 and 78% respectively, while providing a commercially available high sulfur garlic preparation (powder B) at 2% reduced binding by 56%. A pair-feeding study revealed that the depression in carcinogen binding was independent of food intake or weight gain. Although 1% raw garlic powder did not significantly influence the occurrence of DMBA-DNA adducts, an equivalent as the water-extract (0.75%), the ethanol-extract (0.015%) or commercially available powders (A and B) reduced DMBA adducts in mammary tissue by 44, 25, 71 and 65% respectively. Dietary fortification with S-allylcysteine (SAC), a water-soluble constituent of processed garlic, caused a progressive decrease in the binding of DMBA to DNA. Studies with SAC suggest the primary effect of garlic and its constituents is on the bioactivation and binding of the carcinogen rather than DNA repair. These data reveal that several forms of garlic are effective, although variable, in altering carcinogen bioactivation and presumably chemically induced carcinogenesis.