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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: It is indicated that Concord grape juice constituents can inhibit the promotion stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis, in part by suppressing cell proliferation.
Abstract: The effects of Concord grape juice constituents on the promotion of chemically induced rat mammary tumor development and on the proliferation of a rat mammary adenocarcinoma cell line were studied. Isocaloric grape juice formulations provided in the drinking fluid of rats at concentrations of 489 and 651 mg of phenolics/dL of fluid significantly inhibited mammary adenocarcinoma multiplicity compared to controls. Final tumor mass also was significantly decreased for animals provided these two grape juice concentrations compared to controls. In addition, DNA synthesis of the rat mammary adenocarcinoma RBA cell line was significantly inhibited in a dose-dependent manner for cells treated with a grape extract, with an IC50 dose of ∼14 μg of phenolics/mL. This inhibition of DNA synthesis was not accompanied by changes in 8-oxodeoxyguanosine formation or by substantial cell cycle arrest. These studies thus indicate that Concord grape juice constituents can inhibit the promotion stage of 7,12-dimethylbenz[a]anth...
85 citations
TL;DR: Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.
Abstract: 7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides. Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted. Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized. 7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H(3) into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated. The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.
83 citations
Journal Article•
TL;DR: The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.
Abstract: Introduction: Oral carcinoma accounts for 40–50 percent of all cancers in India Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA) -induced hamster buccal pouch carcinogenesis Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 05 percent DMBA in liquid paraffin, three times a week for 14 weeks The tumour incidence, tumour volume and burden were determined in the buccal pouches The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods
82 citations
TL;DR: Cytochrome P-450d, a minor MC-inducible form, has far lower activity for metabolism of both polycyclic aromatic hydrocarbons (PAH), yet also forms high affinity complexes with both PAH, retaining the full high spin state of the free cytochrome.
Abstract: Seven different forms of cytochrome P-450 have been purified from rat liver microsomes. The major 3-methylcholanthrene (MC) inducible cytochrome P-450 (form c) exhibits the greatest activity toward both benzo[a]pyrene (BP) (58 min-1) and 7,12-dimethylbenz[a]anthracene (DMBA) (29 min-1) and forms substantially high spin, high affinity complexes (Kd = 10 nM) with both hydrocarbons. Cytochrome P-450d, a minor MC-inducible form, has far lower activity for metabolism of both polycyclic aromatic hydrocarbons (PAH), yet also forms high affinity complexes (Kd approximately 100 nM) with both PAH, retaining the full high spin state of the free cytochrome. Although two phenobarbital (PB)-induced forms (P-450's b and e) differ by only 13 amino acids, they exhibit significant differences in metabolism of PAH and in complex formation. Whereas P-450b is only active in metabolism of DMBA (9.8 min-1 versus 1.9 min-1 for BP), P-450e has low activity for both substrates (3.3 and 1.2 min-1). Nevertheless, P-450e forms a high affinity complex (Kd approximately 100 nM) with both PAH that enhances the proportion of the high spin state (from 30% to 70%). Failure to displace n-octylamine (NOA) suggests binding that is removed from the heme. P-450b remains low spin in the presence of PAH and NOA is again not displaced. In addition, the two forms can be distinguished by their regioselectivities for both PAH. P-450's a, h, and pregnenolone-16 alpha-carbonitrile (PCN) exhibit little activity toward BP or DMBA, but P-450 PCN does form a low spin complex with BP (not DMBA). Regioselectivity in metabolism of DMBA by PB-induced microsomes does not agree with that of the major constituent forms. Only the minor, less active purified forms (e and a) mediate substantial 12-hydroxylation and 3,4-epoxidation of DMBA. Thus, additional factors in microsomal reactions must contribute to these differences.
82 citations
TL;DR: It is demonstrated that supplemental selenium inhibits both chemical-and viral-induced mouse mammary tumorigenesis, and that the development of preneoplastic lesions, an early stage in mammary tumorsigenisation, is very sensitive to seLenium-mediated inhibition.
Abstract: The effect of supplemental selenium on 7,12-dimethylbenz[a] anthracene (DMBA)-induced mammary tumorigenesis was investigated in several mouse strains. Selenium, administered as SeO2 in the drinking water, inhibited mammary tumor formation in DMBA-treated (C57BL x DBA/2f)F1, C3H/StWi and BALB/c female mice. In addition, selenium inhibited the occurrence of DMBA-induced ductal hyperplasias in (C57BL x DBA/2f)F1 and BALB/c mice and mammary tumour virus-induced alveolar hyperplasias in BALB/cfC3H mice. Selenium did not alter the growth of established mammary tumors. These results demonstrate that supplemental selenium inhibits both chemical-and viral-induced mouse mammary tumorigenesis, and secondly, that the development of preneoplastic lesions, an early stage in mammary tumorigenesis, is very sensitive to selenium-mediated inhibition.
82 citations