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.

Anatomical and Functional Vascular Changes in Hamster Cheek Pouch during Carcinogenesis Induced by 7,12-Dimethylbenz(a)anthracene

Abstract: Anatomical and functional vascular changes during hamster cheek pouch carcinogenesis were studied by light microscopy; scanning electron microscopy of vascular casts; transmission electron microscopy of cheek pouch capillaries; and fractional distributions of 51 Cr-erythrocytes, 125 I-human serum albumin, and 86 RbCl which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Syrian hamsters received 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) in mineral oil for 11 weeks and were sacrificed at periodic intervals from 2 to 20 weeks after initial treatment. Simple hyperplasia was first seen at Week 1. The area of hyperplastic epithelium, expressed as percentage, increased to about 60% by Week 8 and then decreased to 30% at Week 20. Dysplastic foci were first seen at Week 2. The percentage of the area of dysplasia increased with time to 41% at Week 20. Squamous cell carcinomas occurred from Week 10, increased with time, and were found in all animals at Week 20. Vascular cast diameters of normal-looking capillaries were larger during than after DMBA treatment. Type 3 vascular proliferations were found beneath dysplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath dysplasia and cancers were dilated but not fenestrated. Changes in vascular volume were independent of changes in permeability and perfusion and also occurred in contralateral untreated pouches of treated animals. While 86 Rb values initially correlated with 125 I values, the 86 Rb values were unstable in intermediate and later time periods. Changes of vascular volume were accompanied initially by the presence of DMBA and were coincident with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath dysplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. DMBA may lastingly alter capillary endothelium in a manner which allows or aids in its subsequent dilatory and proliferative responses to angiogenic stimulation from malignant tumors, and possibly from premalignant or malignantly transformed cells.

In vitro metabolism of 7,12-dimethylbenz[a]anthracene in mammary epithelial cells from rats with different susceptibilities to carcinogenesis

Abstract: These in vitro metabolism studies of 7,12-dimethylbenz[a]anthracene (DMBA) by rat mammary epithelial cells were initiated to determine whether differences in the incidence of DMBA-induced mammary carcinomas observed between young virgin, old virgin and parous Sprague-Dawley rats can be explained through variations in their ability to metabolize DMBA. The results show that: (a) qualitatively, the metabolic profiles produced by epithelial cells from the 3 groups of rats were similar; (b) the level of metabolism with cells from young virgin and parous rats was similar but was 1.5-2.0 times higher than that obtained with cells from old virgin rats; c) the major ethyl acetate-soluble metabolite detected by h.p.l.c. from cells of old virgin and parous rats was the trans-8,9-dihydrodiol (50-65% of total metabolites), whereas the majority of the radioactivity following incubation with cells from young virgin rats co-eluted with very polar metabolites (65% of total metabolites); and (d) the amount of phenolic metabolites produced by young virgin rat cells was higher than in old virgin or parous rat cells. The data suggest that the susceptibility of young virgin rat mammary cells to DMBA may be due in part to the conversion of a greater percentage of DMBA to phenolic compounds and to water- and ethyl acetate-soluble polar metabolites, and event known to influence the susceptibility of cultured cells to the cytotoxic effects of DMBA.

Biotransformation of 7,12-dimethylbenz [a] anthracene by mouse epidermal cells in culture

Abstract: The formation of cell- and medium-associated metabolites of 7,12-dimethylbenz[a]anthracene (DMBA) by primary mouse epidermal cells was examined using high-pressure liquid chromatography. Cells were cultured in the presence of 14C DMBA for various time periods prior to harvesting. Ethyl acetate/acetone (2:1) extractable metabolites found associated with cells cochromatographed with 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHM-12-MBA), 12-hydroxymethyl-7-methylbenz[a]anthracene (12-OHM-7-MBA), (+/-)-trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz[a]anthracene ((+/-)-trans-DMBA-3,4-diol) and phenols. The major metabolite(s) found within cells cochromatographed with DMBA-phenol(s). Ethyl acetate/acetone extractable metabolites found in the medium cochromatographed with 7-OHM-12-MBA, 12-OHM-7-MBA, (+/-)-trans-DMBA-3,4-diol, (+/-)-trans-8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz[a]anthracene ((+/-) -trans-DMBA-8,9-diol) and phenols. The major ethyl acetate/acetone soluble metabolite found in the medium cochromatographed with (+/-)-trans-DMBA-8,9-diol. This metabolite is rapidly excreted unchanged from the cells into the medium. In addition, primary epidermal cells rapidly converted 14C DMBA to water soluble metabolites that could not be extracted from the medium with ethyl acetate/acetone. Approximately 50% of these water soluble metabolites were extractable with organic solvent upon treatment of the medium with beta-glucuronidase. Phenolic metabolite(s) represented 75-85% of the total beta-glucuronidase releasable material. The results indicated that primary mouse epidermal cells in culture rapdly converted DMBA to a variety of hydroxylated products some of which were conjugated with glucuronic acid. In addition, the formation of (+/-)-trans-DMBA-3,4-diol and its retention within the cells provides additional support for an important role for this metabolite in carcinogenesis by DMBA.

The effect of age on the histopathogenesis of 7,12‐dimethylbenz(a)‐anthracene‐induced mammary tumors in the lewis rat

Abstract: The influence of age at time of DMBA administration on (l) the histopathogenesis and site of mammary tumor origin and (2) the precancerous nature of DMBA-induced mammary dysplasias was examined in Lewis rats between 25 and 200 days of age. Rats were killed at various times after carcinogen treatment and the numbers of tumors and dysplasias were recorded from microscopic examination of mammary gland wholemounts. We found that, in all age-groups tested, mammary tumors always appeared to originate within mammary end-buds and terminal ductules and that terminal due-tule hyperplasia appeared to be an early stage in tumor formation. Age-related differences in susceptibility to tumor development were paralleled by similar differences in susceptibility to the development of terminal ductule hyperplasias. In contrast, although age-related differences in susceptibility to the development of hyperplastic alveolar nodules were also noted, they did not correspond to those observed for tumor development. Thus, hyperplastic alveolar nodules did not appear to be a site of tumor origin in situ or directly related to tumor development.