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.

Gene expression profiling in the mammary gland of rats treated with 7,12-dimethylbenz[a]anthracene.

Abstract: Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real-time PCR, RT-PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of β-casein and transferrin and higher expression of hsp27 in glands from DMBA-treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki-67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, α-tubulin and hsp27, were all overexpressed in the mammary gland of DMBA-treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley-Liss, Inc.

Black tea polyphenols protect against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

Abstract: Dietary chemoprevention has emerged as a cost-effective approach for cancer control. We evaluated the chemopreventive effects of black tea polyphenols (Polyphenon-B) administration during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The expression of proliferating cell nuclear antigen (PCNA) in the buccal pouch and the concentration of lipid peroxides, protein carbonyl, and the antioxidant status in the buccal pouch, liver and erythrocytes were used as biomarkers of chemoprevention. All the hamsters painted with DMBA alone for 14 weeks developed buccal pouch carcinomas associated with increased expression of PCNA, diminished lipid and protein oxidation, and enhanced antioxidant status. In the liver and erythrocytes of tumor-bearing animals, enhanced oxidation of lipids and proteins was accompanied by compromised antioxidant defenses. Dietary administration of Polyphenon-B effectively suppressed DMBA-induced HBP carcinogenesis as revealed by decreased incidence of tumours and PCNA expression. In addition, Polyphenon-B modulated lipid and protein oxidation and enhanced the antioxidant status in the pouch, liver, and erythrocytes. We suggest that Polyphenon-B exerts its chemopreventive effects by inhibiting cell proliferation in the target tissue and modulating the oxidant-antioxidant status in the target as well as in host tissues.

Histologic characterization of rat ovarian carcinoma induced by intraovarian insertion of a 7,12-dimethylbenz[a]anthracene-coated suture: common epithelial tumors of the ovary in rats?

Abstract: BACKGROUND The surface epithelium of the human ovary simulates the mullerian form in tumor formation. In experimental animals, however, such a phenomenon has not previously been observed. METHODS A chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was heated, and the central portion of a 3-0 silk suture was immersed in the melted carcinogen. After vaginal cytology, the DMBA-coated silk was inserted into the ovaries of 40 Wistar strain rats age 7 weeks. The animals were sacrificed when a tumor mass became large enough to extend the abdominal wall. The experimental period lasted for 60 weeks. The tumor histology was compared with that in human counterparts and the mullerian derivatives in rats. RESULTS In 19 rats, including 4 animals with cornified vaginal smears at the time of DMBA treatment, an ovarian carcinoma developed within 36 weeks. In 17 epithelial tumors, the neoplastic cells proliferated to form papillary or glandular structures, and the lining epithelium consisted of flattened or cuboidal cells and columnar cells, often with pseudostratified nuclei. Adenocarcinoma components transformed into squamous cells in two cases. The remaining two neoplasms were pure mesenchymal tumors with histology of a fibrosarcomatous tumor, and one of them contained heterologous malignant osteoid components. In the remaining 21 rats, including 5 with cornified smears, no tumors developed during the experimental period. CONCLUSIONS The histologies of DMBA-induced rat ovarian carcinoma simulated the epithelia of rat ovarian surface, fallopian tube, endometrium, and uterine cervix. The results of this study suggest that the surface epithelium of rat ovary also simulates the mullerian form in tumor formation. Cancer 1998;83:965-970. © 1998 American Cancer Society.