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.

Lupeol, A Bioactive Triterpene, Prevents Tumor Formation During 7,12-Dimethylbenz(a)anthracene Induced Oral Carcinogenesis

Abstract: The oral cancer chemopreventive efficacy of lupeol, a bioactive triterpene, was assessed by monitoring the tumor incidence and using the status of phase I and II xenobiotic metabolizing enzymes, lipid peroxidation and antioxidants as biochemical end points during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA three times a week for 14 weeks. Well differentiated oral squamous cell carcinoma with marked abnormalities in the status of biochemical markers were noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely inhibited the formation of oral tumors and restored the status of biochemical markers during DMBA induced oral carcinogenesis. The present study thus demonstrates the chemopreventive potential of lupeol in DMBA induced oral carcinogenesis. The chemopreventive potential of lupeol is probably due to its antioxidant or free radical scavenging property and modulating effect on phase I and II xenobiotic metabolizing enzymes in favour of the excretion of carcinogenic metabolites during DMBA induced hamster buccal pouch carcinogenesis.

Expression of the angiogenic phenotype by a subpopulation of keratinocytes derived from 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium.

Abstract: The evolution of squamous epithelial neoplasms induced by 7,12-dimethylbenz[a]anthracene (DMBA) in Syrian hamster buccal pouch epithelium (HBPE) and the angiogenic potential of a subpopulation of presumptive preneoplastic keratinocytes was evaluated by examining the ability of whole cell dissociates of HBPE and subpopulations of keratinocytes, or their 72-h serum-free conditioned media (CM), to induce neovascularization in rat corneas and directional migration of bovine adrenal gland capillary endothelial cells (BCE) in culture. Buccal pouches were treated in vivo twice weekly for 5 weeks with either DMBA, paraffin oil (PO) or received no treatment. Hamsters were killed at various times after the last application of carcinogen and single-cell suspensions were prepared by enzymatic dissociation. Angiogenesis was assayed by injecting HBPE cells, or by implanting Hydron pellets containing CM in corneas and observing directional ingrowth of capillary blood vessels. Directional migration of BCE under agarose was tested with CM. Angiogenic activity of DMBA-initiated HBPE dissociates was detected initially at 4 and 5 weeks after treatment, was markedly depressed between weeks 8 and 16 and re-emerged in squamous papillomas at week 25. The pattern of expression of angiogenic activity was observed to parallel the frequency of development of a morphologically unique population of keratinocytes that was detected exclusively in cultures of DMBA-exposed HBPE. These unique cells, designated type II keratinocytes, potently stimulated neovascularization in vivo and directional migration of BCE in culture. These results demonstrate that angiogenic activity is an early manifestation of hamster pouch carcinogenesis and suggests that type II keratinocytes, presumptive preneoplastic cells in this model, are the principal source of this activity.

Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats.

Abstract: Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA)-induced mammary cancer in female Sprague-Dawley (SD) rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg) through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p) were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phase I and Phase II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumour markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

Distribution of covalent DNA adducts in mouse epidermal subpopulations after topical application of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene.

Abstract: The distribution of benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene (DMBA):DNA adducts was examined in five different subpopulations of SENCAR mouse epidermal cells separated based on buoyant density in continuous gradients of 61.5% Percoll. Three fractions consisted of primarily basal cells (Fractions 3 to 5), while two less dense fractions (Fractions 1 and 2) consisted of primarily differentiating keratinocytes. The levels of B(a)P and DMBA:DNA adducts were examined at 1 h, 6 h, 24 h, 72 h (except DMBA), and 28 days after a single topical application of an initiating dose. Among the basal cell subpopulations, the level of covalent B(a)P:DNA adducts in Fraction 5 cells was significantly higher (P less than 0.05) than Fractions 3 and 4 at every time point examined. On the other hand, B(a)P:DNA adduct levels in Fraction 5 were only significantly higher than Fraction 2 at 6 h and 72 h and not significantly different from Fraction 1 at any time point. With DMBA, no significant differences were initially observed in the levels of covalent DNA adducts among the various Percoll fractions at 1 h and 6 h after treatment. However, at 24 h and at 28 days. Fraction 5 cells had significantly higher (P less than 0.05) levels of covalent DMBA:DNA adducts than Fractions 1 to 4. To explore whether the observed differences in DNA adduct levels were due to differences in metabolic activation, we examined the levels of covalent adducts among epidermal subpopulations after topical application of (+/-)-anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (anti-BPDE). Interestingly, 3 h after treatment with anti-BPDE, significantly higher (P less than 0.05) levels of binding were found in Fraction 5 compared with Fractions 1 to 4. High-pressure liquid chromatographic analyses of B(a)P and DMBA:DNA adducts 6 h and 24 h after treatment did not show any significant differences in adduct profiles among the various subpopulations. These results demonstrate the presence and persistence of hydrocarbon:DNA adducts in all epidermal subpopulations isolated on continuous Percoll gradients for at least 28 days after treatment. Furthermore, of the three basal cell subpopulations, the most dense cells (Fraction 5) developed the highest DNA adduct levels within 24 h and retained these higher levels over 28 days. Finally, differences in DNA adduct levels among epidermal subpopulations do not appear to result from different metabolic capabilities of the cells. The potential significance of these results is discussed in terms of the process of skin tumor initiation.