7,12-Dimethylbenz anthracene DMBA

Singletary, K.W., and J.M. Nelshojjpen. 1991. Inhibition of 7,12-dimethylbenz[ ]anthracene (DMBA)-induced mammary tumorigenesis and of in vivo formation of mammary DMBA-DNA adducts by rosemary extract. Cancer Lett. 60(2) 169-175. 

As mentioned earlier that sesame lignans, especially sesamin and epi-sesamin, could influence the metabolism of polyunsaturated fatty acid and the production of prostaglandins. As prostaglandin is one of the most influential factors for mammary carcinogenesis, Hirose et al. (99) studied the effect of sesamin on dimethylbenz-anthracene (DMBA)-induced mammary cancer. Their results showed that sesamin at a dietary level of 0.2% considerably reduced the cumulative number and mean number of mammary cancer the effectiveness of sesamin was similar to a-tocopherol. 

Jung KJ, Wallig MA and Singletary KW. 2006. Purple grape juice inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett 233 279-288. 

Schnitz, A.R. and J.M. O Connor. 1992. In vivo DNA/RNA adduction of 7, 12-dimethylbenz(a)anthracene (DMBA) and benzo[a]pyrene (BaP) in the liver of rainbow trout (Oncorhynchus mykiss). Jour. Environ. Pathol. Toxicol. Oncol. 11 229-233. 

Li S, Levesque C, Geng CS, Yan X, Labrie F (1995) Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen EM-219 on estrone (El)-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Breast Cancer Res Treat 34 147-159... 

No effects on survival were observed in mice treated dermally with an unspecified volume of 5% phenol (3 times/week) or 10% phenol (2 times/week) in acetone for 12 months (Wynder and Hoffmann 1961). Pretreatment with a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) followed by phenol resulted in increased skin tumors and decreased survival. 

Constantinou AI, Mehta R, Husband A. (2003) Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Fur J Cancer 39 1012-1018. 

In vivo, letrozole (3) was efficacious in two animal models. One was a postmenopausal hormone-dependent breast cancer mouse model, the other was a dimethylbenz[a]-anthracene (DMBA)-induced mammary carcinoma rat model. 

Anticarcinogenic Activity of CLA. Anticarcinogenic activity of synthetically prepared CLA was first tested in the two-stage mouse epidermal carcinogenesis model. In this study, 7 days, 3 days, and 5 min prior to 7,12-dimethylbenz[a]anthracene (DMBA) application, CLA was applied directly on the shaved backs of individual mice at doses of20,20, and 10 mg, respectively (7). Control mice were treated similarly with linoleic acid or acetone. All mice were given TPA to effect tumor promotion. It was found that CLA treated mice developed only about half as many papillomas and exhibited a lower tumor incidence than control mice. 

Benzoyl peroxide was tested for promoting activity in groups of 20 and 15 female SEN mice receiving a single topical application of 20 nmol 7,12-dimethylbenz[rz]anthracene (DMBA) followed by either 0.2 inL of a 100 ing/inL solution of benzoyl peroxide in acetone or acetone alone for 51 weeks. At the termination of the experiment, there were no skin tumours among the 15 control mice, compared with 20/20 in the benzoyl peroxide-treated mice p < 0.01), of which 18/20 were squamous-cell carcinomas. The first tumour developed in week 8. All 20 treated mice showed epidennal hyperplasia (Kurokawa et al., 1984). 

Groups of 20 female NMRI mice, seven weeks of age, received a single skin application of either (o) 100 nmol 7,12-dimethylbenz[fl]anthracene (DMBA), (Z ) 100 pmol methyl methanesulfonate or (c) 400 piuol methyl methanesulfonate (highest tolerated dose). One week later, all were treated with 10 nmol 12-i9-tetradecanoylphorbol 13-acetate twice weekly for 24 weeks. While 90% of the DMBA group had skin tumours after 15 weeks, no methyl methanesulfonate-initiated mice had skin tumours after 24 weeks (Fiirstenberger et al., 1989). 

My interest in the influence of diet on hormone-dependent cancers was first stimulated about 20 years ago by studies carried out in collaboration with colleagues at the Collip Medical Research Laboratory of the University of Western Ontario. They were involved in studies on the role of hormones in mammary cancer and for this purpose were inducing tumors in rats with 7,12-dimethylbenz(oi)-anthracene (DMBA) as described by Huggins et al ( 1). They were concerned to know whether hormonal treatment might affect tumorigenesis by altering the degree and time of exposure of mammary... 

Our laboratory has completed a series of studies designed to evaluate the simultaneous effects of dietary protein and fat on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in rats. Sprague-Dawley female rats were assigned to nine diets in a 3 x 3 factorial arrangement with protein (casein) at 8, 16, and 32% of kcals and fat (corn oil) at 12, 24, and 48% of kcals. As fat content was increased, all nutrients other than carbohydrate were adjusted to remain constant with respect to calories. Forty rats were assigned to each diet for each of three experiments (Figure 1) to examine initiation, promotion, and the combined phases of chemically-induced carcinogenesis. 

Dimethylbenz( a) anthracene (DMBA)-induced mammary carcinoma in the rat is a widely used animal model to study the factors that control hormone-sensitive breast cancer in women. In fact, the development and growth of these tumors are particularly sensitive to the stimulatory action of estrogen and prolactin (Asselin et al., 1977 Asselin and Labrie, 1978 Dauvois and Labrie, 1990 Dauvois et al., 1989b Huggins et al., 1961 Jordan and Allen, 1980 Kelly et al., 1977, 1979 Labrie et al., 1976, 1993 Leung etal., 1975 Li et al., 1993, 1995 Welsch, 1985). 

Fig. 19. Effect of treatment with dehydroepiandrosterone (DHEA) (10 mg, percuta-neously, once daily) or EM-800 (75 pg, orally, once daily) alone or in combination for 9 months on the incidence of dimethylbenz (a) anthracene (DMBA)-induced mammary carcinoma in the rat throughout the 279-day observation period. Data are expressed as percentage of the total number of animals in each group (Luo et al., 1997c).

Mam-2 Inhibition of 7,12-dimethylbenz[a (anthracene (DMBA) induced mammary tumors... 

In the initial study by Ip et al. (1991), the authors fed rats a standard diet or that diet supplemented with 0.5, 1.0 or 1.5% CLA, 2 weeks prior to and following administration of the carcinogen 7, 12-dimethylbenz[a]anthracene (DMBA). At the end of the experiment, the total number of mammary adenocarcinomas in the groups fed 0.5, 1.0 and 1.5% CLA was reduced by 32, 56 and 60% compared to the control, respectively. Tumor incidence, tumor multiplicity (number of tumors per rat) and total tumor weight were reduced to a similar degree. This tumor inhibition by CLA is in contrast to linoleic acid, which promotes tumor development in this model. 

Dimethylbenz [a] anthracene (DMBA)—induces mutations at the TK locus with metabolic activation... 

FIGURE 12.17. (a) Chemical formula and (b) stereoview of 7,12-dimethylbenz[ a ]-anthracene (DMBA), showing the buckling of the molecule as a result of the presence of the 12-methyl group (Refs. 48 and 49). 

Application of rosemary to mouse skin inhibited covalent binding of benzo(a)pyrene to epidermal DNA and inhibited tumor initiation by benzo(a)pyrene [B(a)P] and 7,12-dimethylbenz(a)anthracene (DMBA). Topical application of 1, 3 or 10 pmol camosol together with 5 nmol 12-0-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63 and 78%, respectively. 

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