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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.
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TL;DR: Genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA, and this response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.
52 citations
TL;DR: The possible beneficial effect of morin as chemopreventive agent against the oxidative stress induced during mammary carcinogenesis is revealed.
Abstract: In general, oxidative stress resulting from an imbalance between prooxidant and antioxidant systems plays an important role in the pathogenesis of cancer. Morin (3,5,7,2′,4′-pentahydroxyflavone), a member of the flavanol group, has been shown to possess chemopreventive potential against hepatocellular and colon cancer in experimental animals. Given the demonstrated importance of morin, aim of the present study was to evaluate the effect of morin on antiproliferative and anticarcinogenic effect against DMBA-induced experimental mammary carcinogenesis. Oral administration of 7,12-dimethylbenz(a)-anthracene (25 mg/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and nonenzymic antioxidants (reduced glutathione, vitamin C, and vitamin E). The levels of lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) and tumor markers such as CA 15-3, AFP and CEA in serum were increased significantly in cancer-induced animals as compared to control rats. Oral supplementation of morin at a dose of 50 mg/kg body weight significantly improved the body weight, enzymic, and nonenzymic antioxidants and considerably decreased the lipid peroxidation marker and tumor markers levels. Histological observations also correlated with the biochemical parameters. Tumor bearing animals showed marked increase in proliferating cell nuclear antigen-positive cells and also the number of AgNOR/nuclei compared with control rats while this expression levels were significantly reduced upon morin treatment. Thus, this study reveals the possible beneficial effect of morin as chemopreventive agent against the oxidative stress induced during mammary carcinogenesis.
52 citations
Journal Article•
TL;DR: The experimental production of mammary tumors by administration of 7,12-dimethylbenz(a)anthracene was confirmed, and it was suggested that the lack of metastasis is related to several factors, all of which need further study.
Abstract: The experimental production of mammary tumors by administration of 7,12-dimethylbenz(a)anthracene was confirmed. Light microscopic examination of the multiple tumors thus produced showed different histological patterns in the same animal, although all tumors behaved similarly and none metastasized. Both epithelial and myoepithelial cells participated in tumor formation; the stroma also participated actively in tumor formation and growth. Unlike the case in human myoepithelial carcinoma of the breast, the enzyme alkaline phosphatase continued to be reactive on the plasma membrane of the proliferating myoepithelial cells. It is suggested that the lack of metastasis is related to several factors, all of which need further study. These factors include the simultaneous proliferation of myoepithelial and epithelial cells, the persistence of alkaline phosphatase on the plasma membrane of myoepithelial cells, and the infiltration of the tumor by mast cells.
51 citations
TL;DR: It is demonstrated that the effect of DMBA on bone marrow cellularity is p53-dependent, and apoptosis of primary cultures of progenitor B cells cultured with bone marrow stromal cells and DMBA is also p 53-dependent.
51 citations
TL;DR: It is shown that bone marrow stromal cells metabolize DMBA to such products as 3,4-dihydrodiol, the precursor to the most mutagenic DMBA metabolite.
Abstract: The polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA) is a potent carcinogen that produces immunotoxic effects in bone marrow. Here, we show that bone marrow stromal cells metabolize DMBA to such products as 3,4-dihydrodiol, the precursor to the most mutagenic DMBA metabolite. The BMS2 bone marrow stromal cell line constitutively expressed higher levels of CYP1B1 protein and mRNA than C3H10T½ mouse embryo fibroblasts. BMS2 cells also produced a DMBA metabolite profile that was consistent with CYP1B1 activity. Treatment with the potent aryl hydrocarbon receptor (AhR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced a ∼2-fold increase in CYP1B1 mRNA, protein, and activity in BMS2 cells. Two forms of the AhR (97 and 104 kDa) and the AhR nuclear translocator were detected in BMS2 cells. The AhR translocated to the nucleus after treatment with TCDD or DMBA but was ∼5 times slower with DMBA. Primary bone marrow stromal (BMS) cell cultures established from AhR−/− mice showed similar basal CYP1B1 expression and activity as cell cultures established from heterozygous littermates or C57BL/6 mice. However, primary BMS cells from AhR−/− mice did not exhibit increased CYP1B1 protein expression after incubation with TCDD. BMS cells therefore constitutively express functional CYP1B1 that is not dependent on the AhR. This contrasts with embryo fibroblasts from the same mouse strain, in which basal CYP1B1 expression is AhR dependent. We therefore conclude that bone marrow toxicity may be mediated by CYP1B1-dependent DMBA metabolism, which is regulated by factors other than the AhR.
51 citations