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.

A comparison of the effects of the prostaglandin synthesis inhibitors indomethacin and carprofen on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis in rats fed different amounts of essential fatty acid.

Abstract: The effects of the cyclooxygenase inhibitors indomethacin and carprofen on the enhancement of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis by dietary linoleate have been compared in female Sprague-Dawley rats. Indomethacin and carprofen, 0.004% and 0.02% (w/w) in the diet, respectively, were fed to rats receiving 20% fat diets containing 0.5, 4 or 12% linoleate starting 7 days after administration of 5 mg DMBA i.g. Indomethacin was shown to have a marked inhibitory effect on mammary tumorigenesis in rats fed the 4 and 12% linoleate diets, but did not alter tumorigenesis in rats fed the 0.5% linoleate diet. In contrast, carprofen was not inhibitory in any of these dietary groups, or in a separate experiment in which a 5% fat--3% linoleate diet was fed. The effect of each drug on prostaglandin E2 (PGE2) levels in normal mammary glands enriched in epithelial cells after a 3-week pretreatment with 17 beta-estradiol and progesterone was also investigated. Carprofen was shown to reduce PGE2 levels to a similar or greater extent than indomethacin at each level of linoleate in the diet. These data demonstrate that a reduction in PGE2 synthesis in the mammary epithelium does not correlate with inhibition of mammary tumorigenesis, and that other factors, including possible alterations in other products of the arachidonic acid cascade, are responsible for this inhibitory effect.

Rapid Induction of γ-Glutamyl Transpeptidase-rich Intraepithelial Clones in 7,12-Dimethylbenz(a)anthracene-treated Hamster Buccal Pouch

Abstract: Individual γ-glutamyl transpeptidase (GGT)-stained cells and cell doublets were rapidly induced in the epithelium of hamster buccal pouch treated with biweekly topical applications of 0.5% 7,12-dimethylbenz(a)anthracene (DMBA) in mineral oil. The cells were detected histochemically in whole mounts of pouch epithelium harvested as early as 3 days after the first application of this carcinogen. During 3 consecutive weeks of DMBA treatment, progressively larger GGT-stained epithelial cell populations (plaques) up to 0.5 mm in diameter were encountered. Similar GGT-stained lesions were not detected in whole mounts of untreated epithelium and were rarely seen in GGT-stained whole mounts prepared from mineral oil-treated pouch epithelium. In an experiment designed to assess the stability of the GGT-staining pattern, very few plaques could be detected 12 weeks after a 3-week regimen of six DMBA applications. However, data are presented suggesting that a brief series of three DMBA applications reinduced GGT histochemical activity in occult intraepithelial plaques, which had lost enzyme activity but had persisted over an 11-week treatment-free interval. The clonal nature of the GGT-stained plaques and their apparent ability to persist in an occult form for several weeks or months lend further support to the hypothesis that these carcinogenaltered cell populations may be potential precursors for the development of squamous epithelial neoplasia.

β-Carotene Prevention of 7,12-Dimethylbenz [A] Anthracene-Induced Transformation of Mouse Mammary Cells In Vitro

Abstract: Epidemiological studies have suggested that β-carotene, a dietary vitamin A precursor, may influence reduced tumor incidence in human populations1. In contrast to the abundance of studies2,3 on the chemopreventive properties of retinoids (vitamin A analogues) little is known about the mode of action of β-carotene, the vitamin A precursor. Only a few preliminary reports based on rather indirect observations have indicated that a carrot rich diet or injections of β-carotene result in reduced tumor incidence in rats and mice treated with a carcinogenic chemicals and/or u.v. radiation4–6. These observations prompted the investigations of the chemopreventive role of β-carotene itself in an in vitro controlled environment, because in the animal the vitamin A precursor is metabolized to retinol.