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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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Journal ArticleDOI
TL;DR: It is demonstrated that RIalpha antisense produces dual anticarcinogenic effects: increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and activating DNA repair processes in the mammary gland by down-regulating PKA-I.
Abstract: Purpose: There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIα) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIα gene expression at the initial phase of 7,12-dimethylbenz(αa)anthracene (DMBA)-induced mammary carcinogenesis. Experimental Design: Antisense RIα oligodeoxynucleotide (ODN) targeted against PKA RIα was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Results: Antisense RIα, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIα-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIα and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIα restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIα in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIα promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIα. Conclusions: The results demonstrate that RIα antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I.

16 citations

Journal ArticleDOI
TL;DR: The structure of the adducts was elucidated by using UV, NMR, and MS and it was found that the N-7 positions in dG, dA, and Ade, the 2-NH2 indG, and the N1 position in Ade form exclusively methyl-linked adductS.
Abstract: Study of DNA adducts formed with aromatic hydrocarbons is part of the strategy to elucidate the mechanisms of tumor initiation by these compounds. 1,2,3,4-Tetrahydro-7,12-dimethylbenz[a]anthracene ...

16 citations

Journal ArticleDOI
TL;DR: Experiments on the use of chronically applied restraint to reduce the number of mammary tumors developing in response to treatment of rats with 7,12-dimethylbenz[a]anthracene indicated that this inhibitory effect was largely due to restraint applied after the induction period; preinduction restraint and induction period restraint had no significant effect on tumor development.
Abstract: Experiments on the use of chronically applied restraint to reduce the number of mammary tumors developing in response to treatment of rats with 7,12-dimethylbenz[a]anthracene indicated that this inhibitory effect was largely due to restraint applied after the induction period; preinduction restraint and induction period restraint had no significant effect on tumor development. After termination of the restraint treatment, the rate at which new tumors appeared first increased and then decreased. Restraint did not affect the proportion of tumors regressing after ovariectomy.

16 citations

Journal Article
TL;DR: The results suggest that the increased total binding and possibly the decreased proportion of syn-diol-epoxide:DNA adducts confer greater tumor-initiating potency on 10-F-DMBA.
Abstract: 10-Fluoro-7,12-dimethylbenz( a )anthracene (10-F-DMBA) is a more potent skin tumor initiator in SENCAR mice when compared with the parent hydrocarbon 7,12-dimethylbenz( a )anthracene (DMBA). To elucidate the mechanism for this difference, the covalent binding of these two hydrocarbons to the DNA of mouse epidermal cells in vivo and in vitro was compared. The quantity of 10-F-DMBA covalently bound to mouse epidermal DNA in vivo was greater than that of DMBA at all doses tested over the range of 4 to 200 nmol/mouse. The magnitude of this binding difference between 10-F-DMBA and DMBA was greater at the higher doses ( e.g. , 1.5-fold at 4 nmol/mouse versus 3.4-fold at 200 nmol/mouse). These results correlated closely with the dose-response relationships for tumor initiation by the two hydrocarbons. Analysis of the isolated DNA samples by Servacel DHB chromatography revealed the relative proportion of syn -diol-epoxide:DNA adducts derived from DMBA increased dramatically as a function of dose (∼30% at 4 nmol/mouse versus ∼55% at 200 nmol/mouse). Conversely, the relative proportion of syn -diol-epoxide adducts derived from 10-F-DMBA was low and remained essentially constant over the same dose range. High-pressure liquid chromatographic analyses of the DNA adducts derived from DMBA- and 10-F-DMBA-treated mice revealed qualitatively similar profiles. However, as expected, there was a marked reduction in the relative proportion of syn -diol-epoxide:DNA adducts in the profiles of epidermal samples from 10-F-DMBA-treated mice. The major syn -diol-epoxide:deoxy-adenosine adduct was present at a level only 30% that found in high-pressure liquid chromatographic profiles of DMBA samples. Similar results were obtained when primary cultures of mouse epidermal cells were treated with the hydrocarbons. The results suggest that the increased total binding and possibly the decreased proportion of syn -diol-epoxide:DNA adducts confer greater tumor-initiating potency on 10-F-DMBA.

16 citations

Journal ArticleDOI
TL;DR: The data suggest that chemicals which depress NKC are likely to enhance susceptibility toMCMV, and conversely that effects on NKC should be suspected when chemical exposure enhances susceptibility to MCMV.

16 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20236
202215
202121
202018
201912
201823