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.

DNA Binding and Inhibition of DNA Synthesis after 7,12-Dimethylbenz(a)anthracene Administered during the Early Prereplicative Phase in Regenerating Rat Liver

Abstract: We have previously reported that 7,12-dimethylbenz(a)anthracene (DMBA), given iv 24 hr after partial hepatectomy when DNA replication is maximal, binds tightly to DNA, inhibits its synthesis, and induces neoplastic changes in regenerating rat liver We now report that DMBA injected iv 5 hr after partial hepatectomy ( ie , during the early prereplicative phase) inhibits DNA synthesis for at least 48 hr The amount of tritiated DMBA bound to DNA by 11 hr equals the maximum amount found in intact rat liver; however, from 11 to 24 hr the amount bound to DNA increases 2- to 3-fold (in untreated regenerating rat liver, DNA synthesis begins 16 hr after partial hepatectomy) In the small in testine, in which DNA synthesis is continuous and relatively constant in rate, the amount of DMBA bound to DNA is maximal by 11 hr The amount of DNA-bound benz(a)anthracene given iv 5 hr after partial hepatectomy decreases from 11 to 24 hr Binding of DMBA in regenerating rat liver persists for at least 4 weeks; in small intestine the amount of DNA-bound carcinogen decreases at a rate suggesting loss by cell renewal It appears that, on entry into the replicative phase, DNA becomes more susceptible to binding and the bound carcinogen persists in surviving cells

DNA sequence analysis of hprt mutations in lymphocytes from Sprague‐Dawley rats treated with 7,12‐dimethylbenz[a]anthracene

Abstract: Treatment of female Sprague-Dawley rats with the potent mammary gland carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) results in the formation of DNA adducts with dG and dA and in the induction of 6-thioguanine-resistant (TGr) lymphocyte mutants In this study, we have examined the types of mutations induced in TGr lymphocytes from DMBA-treated rats DNA from 263 TGr lymphocyte clones was screened for mutations in exons 2, 3, and 8 of the hprt gene by polymerase chain reaction (PCR) amplification of the exons followed by heteroduplex analysis using denaturing gradient-gel electrophoresis Twenty-five of the clones produced heteroduplexes in exon 2, 35 produced heteroduplexes in exon 3, and 36 produced heteroduplexes in exon 8 Direct sequence analysis of the heteroduplexes revealed 96 mutations, and at least 74 of these mutations were produced independently Eighty-five of the total mutations were simple base pair (bp) substitutions, with A --> T and G --> T transversions being the predominant types Seven mutations were deletions, three were complex bp substitutions, and one was an insertion The results suggest that the types of mutations produced by DMBA in rat lymphocytes are specific to the DNA adducts produced by this compound

Saffron Reduction of 7,12-Dimethylbenz[a]anthracene-induced Hamster Buccal Pouch Carcinogenesis

Abstract: Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis.

Analysis of ras gene mutational spectra in epidermal papillomas from K6/ODC transgenic mice

Abstract: In standard mouse strains, a high proportion (more than 90%) of epidermal tumors produced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with a variety of chemical agents contain an activating mutation in codon 61 (A182→T) of the c-Ha-ras gene. We analyzed the ras mutational spectra in 69 tumors induced by DMBA in a unique transgenic model, the K6/ODC mouse. In this model, low-dose DMBA treatment is sufficient per se for tumor induction, so tumor promotion with chemical agents is not required. In contrast to previous studies in standard mouse strains, our study showed that less than 50% of epidermal tumors from K6/ODC mice contained an activating codon 61 c-Ha-ras mutation (A182→T). This result was obtained in mice initiated either as newborns (when the transgene is not expressed) or as adults (when the transgene is fully expressed). Analysis of other codon hot-spots and other ras genes revealed the presence of three codon 12 and 20 codon 61 (A182→T) mutations in the c-Ki-ras gene in the 36 tumors that did not have c-Ha-ras mutations. We concluded that promotion in this model, by means of constitutive ornithine decarboxylase expression, causes the clonal expansion of a population of initiated cells not promoted by chemical agents. Mol. Carcinog. 22:145–149, 1998. © 1998 Wiley-Liss, Inc.