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.

Mode of action of selenium inhibition of 7,12-dimethylbenz[a]anthracene-induced mouse mammary tumorigenesis.

Abstract: Possible mechanisms for the inhibitory effect of selenium on mouse mammary gland tumorigenesis were evaluated in two different mouse models, in 7,12-dimethylbenz[a]anthracene [(DMBA) CAS:57-97-6]treated and hormonally stimulated mammary glands with two dietary levels of Se (0.2 and 2.0 ppm). In (C57BL X DBA/2f)F1 (BD2F1) and BALB/c strains of female mice, Se at 2.0 ppm decreased mammary tumor incidences by 36 and 68%, respectively. Selenium-dependent glutathione peroxidase (GSH-Px) activity in the mammary glands of BD2F1 female mice decreased at 6 months of age and then increased to the highest levels at 9 months of age. Mammary glands from DMBA-treated mice had lower GSH-Px activity than those from control mice. The increase of dietary Se to 2.0 ppm did not overcome this DMBA effect. These results indicate that GSH-Px activity does not correlate with the tumorigenic inhibitory effects of Se. In the hormonally stimulated mammary gland, increasing dietary Se to 2.0 ppm increased GSH-Px activity threefold and decreased mammary-gland-membrane-localized lipid peroxidation by 16%. In vitro peroxidation of hormonally stimulated mammary glands was inversely proportional to the level of GSH present in the incubation mixture. The marginal decrease in lipid peroxidation found in the mammary glands exposed to 2.0 ppm Se could not explain the inhibitory effect of Se on tumorigenesis.

Preferential alteration of inducible gene expression in vivo by carcinogens that induce bulky DNA lesions

Abstract: Our laboratory is interested in whether chemical carcinogen—induced DNA damage is nonrandomly distributed in the genome, i.e., “targeted,” at the level of individual genes. To examine this, we have been investigating whether carcinogen treatment in vivo differentially alters the expression of specific genes. In this study, we examined the effects of four model carcinogens that induce bulky lesions in DNA—benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA), and 2-acetylaminofluorene (AAF)—on the steady-state mRNA expression of several constitutive and drug-inducible genes in vivo. We specifically tested the hypothesis that carcinogen-induced DNA damage is preferentially targeted to inducible genes relative to constitutively expressed genes using the chick embryo as a simple in vivo test system. In summary, the four carcinogens had no effect on the steady-state mRNA expression of constitutively expressed β-actin, transferrin, or albumin genes over a 24-h period after a single dose of each carcinogen. In contrast, each of these same treatments significantly altered the mRNA expression of two glutethimide-inducible genes, ALA synthase and CYP2H1. Both the basal expression of these genes and their drug-inducible expression was altered. B[a]P and AFB1 had similar effects on expression of the two inducible genes and caused similar levels of covalent adducts in total DNA, even though the administered doses differed by 30-fold. B[a]P metabolism, B[a]P binding to DNA, and the basal expression of CYP2H1 were similar in liver and lung. However, B[a]P significantly altered basal CYP2H1 mRNA expression in liver, a tissue in which this gene is highly inducible by glutethimide, and had no effect on basal CYP2H1 mRNA expression in lung, a tissue in which this gene is not drug-inducible. These data support the hypothesis that inducible gene expression is a target for carcinogen-induced DNA damage in vivo. © 1993 Wiley-Liss, Inc.

Protective effect of Picroliv, the active constituent of Picrorhiza kurroa, against chemical carcinogenesis in mice.

Abstract: Cancer chemoprevention of chemically induced tumours by Picroliv, an iridoid glycoside mixture purified from Picrorhiza kurroa, was studied on 20-methylcholanthrene (20-MC)-induced sarcoma model and 7,12-dimethylbenz[a]anthracene (DMBA)-initiated papilloma formation in BALB/c mice. Administration of Picroliv (100 and 200 mg/kg, p.o) inhibited the sarcoma development by 47 and 53% as estimated on day 200 after 20-MC administration. Control animals started dying of tumour burden 76 days after 20-MC administration and all animals were dead by day 170, while 60 and 66% of the animals survived in the Picroliv treated group, 100 and 200 mg/kg, respectively. Picroliv exhibited anti-tumour-promoting activity on a two-stage carcinogenesis test on mouse skin using DMBA as an initiator and croton oil as a promoter. Topical application of Picroliv (1 and 5 mg/mouse) 30 minutes prior to that of croton oil application resulted in a 50 and 60% reduction in the number of animals that developed papillomas, and 48 and 64% reduction in the number of papillomas per mouse. There was also a delay in the onset of first skin tumour in the group of animals treated with Picroliv. Oral administration of Picroliv (150 mg/kg, p.o.) prior to DMBA application delayed the onset of papillomas and the percent of mice (60%) with tumours indicates that Picroliv inhibited the tumour initiation induced by DMBA. Picroliv administration was also found to increase the life span of transplanted Dalton's Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) harboring mice and reduced the volume of transplanted solid tumours.

Skin tumorigenesis by 7,12-dimethylbenz(a)anthracene: inhibition by actinomycin d.

Abstract: Topical application of actinomycin D during a short period of time immediately before and after a single application of 7, 12-dimethyl-benz (a)anthracene markedly inhibits subsequent tumor formation. The results indicate that the initial events of carcinogenesis are dependent on DNA-dependent RNA synthesis.