7,12-Dimethylbenz anthracene skin tumors

The initial studies at RIVM demonstrated that exposure of these mice to IV-B radiation or 7,12-dimethylbenz[a]anthracene resulted in the rapid induction of skin tumors. It was also shown that various internal tumors could be induced following... 

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. 

Short-term dermal studies with 2,3,7,8-TCDD had controversial results. Some studies reported its inhibitory effects on the development of skin tumors in mice otherwise initiated by 13-dimethylbenz-(o)anthracene (Berry et al. 1978, 1979). Others cited its ability to promote tumors initiated by N-methyl-N-nitro-N-nitrosoguanidine (Hebert et al. 1990 Poland et al. 1982). Further, intraperitoneal injection of... 

Data regarding interactions affecting the toxicity or toxicokinetics of other chemicals by 2,3,7,8-TCDD were limited. Dermal pretreatment with 2,3,7,8-TCDD inhibited the induction of skin tumors by subsequently applied benzo(a)pyrene or dimethylbenz(a)anthracene in Senear mice (Cohen et al. 1979). It was proposed that 2,3,7,8-TCDD caused qualitative alteration of hydrogen binding to DNA. In... 

Nishino, H. Okuyama, T. Takata, M. Shibata, S. Tokuda, H. Takayasu, J. Hasegawa, T. Nishino, A. Ueyama, H. Iwashima, A. Studies on the anti-tumor-promoting activity of naturally occurring substances IV. Pd-H [(+)anomalin, (- -)praeruptorin B], a seselin-type coumarin, inhibits the promotion of skin tumor formation by 12-O-tetradecanoyl-phorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated mice. Carcinogenesis (London), 1990, 11 1557-1561. 

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. 

Slaga TJ, Jecker L, Bracken WM, et al. 1979. The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7,12- dimethylbenz(a)anthracene and benzo(a)pyrene skin tumor-initiation. Cancer Lett 7 51-59. 

These results of in vitro experiments prompted us to examine the effect of SDB on carcinogenesis in vivo. From one week after initiation by a sigle application of 7,12-dimethylbenz[a]anthracene (DMBA, 100 mg), 1.62 nmol of TPA was applied twice a week. SDB (162 nmol) was applied simultaneously with each TPA treatment and the number of skin tumors was determined each week. The first tumor appeared at week 6 in the control group, while the appearance of the first tumor was delayed to week 11 in the group treated with SDB. In addition, SDB decreased significantly the average number of tumors per mouse (control group 6... 

Slaga, T.J., A. Viaje, S.G. Duty, and W.M. Bracken Dibenz[a,c]anthracene A potent inhibitor of skin-tumor initiation by 7,12-dimethylbenz[a] anthracene Res. Comm. Chem. Pathol. Pharmacol. 19 (1978) 477-483. Slanki, J.M. and R.J. Moshy Separation and quantitative analysis of polyhydric alcohol humectants in tobacco products J. Chromatog. 35 (1968) 94—98. 

And, many compounds which showed strong inhibitory effects on the induction of EBV-EA by TPA have been shown to act as inhibitors of tumor promotion on two-stage carcinogenesis test in vivo [15-21, 27-29]. The one of two-stage carcinogenesis test is on mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a... 

Nishino, H., Kitagawa, K., and Ito, Y., Antitumor-promoting activity of glycyrrhetic acid in mouse skin tumor formation induced by 7,12-dimethylbenz[a]anthracene plus teleocidin. Carcinogenesis, 5, 1529 (1984). 

Topical application of the compound juglone to mice promoted skin tumors induced with the carcinogen DMBA (7,12-dimethylbenz[fl]anthracene) (Monks et al. 1990 Van Duuren et al. 1978), although no tumors were observed in mice treated with juglone alone (Van Duuren et al. 1978). 

Myricetin has been reported to have a role in anticarcinogenesis. Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, cause skin and lung cancer in experimental animals. Myricetin reduces polycyclic aromatic hydrocarbon-induced tumors in the skin. Topical administration of myricetin provided significant protection against skin tumorige-nicity in SENCAR mice that were given 7,12-dimethylbenz(a)anthra-cene, benzo(a)pyrene and N-methyl-N-nitrosourea as tumor initiators, followed by 12-0-tetradecanoylphorbol-13-acetate as a tumor promoter. Additionally, myricetin delayed onset and subsequent recurrence of skin tumors in BALB/c mice that were administered benzo(a)p5uene, 7,12-dimethylbenz(a)anthracene, and N-methyl-N-nitrosourea as tumor initiators and 3-methyl-cholanthrene as a tumor promoter [19]. 

For example, 7,12-dimethylbenz[a]anthracene is a particularly potent carcinogen for the mammary gland of young female Sprague-Dawley rats after oral or intravenous administration (25,26), dietary benzo[a]pyrene leads to leukemia, lung adenoma and stomach tumors in mice (27), and either of these hydrocarbons can induce hepatomas in male mice when injected on the first day of life (28). Nevertheless, the mouse skin system has proved to be particularly valuable because of the rapidity of tumor induction, the ease of detection of tumors and because the multi-stage nature of the carcinogenic process was experimentally established in this system. 

Schweizer, J., Loehrke, H., Elder. L. Goerttler, K. (1987) Benzoyl peroxide promotes the formation of melanotic tumors in the skin of 7,12-dimethylbenz[a]anthracene-initiated Syrian golden hamsters. Carcinogenesis. 8. 479-482... 

Isotetrandrine was found to inhibit arachidonic acid-induced inflammation in mice. Topical application of isotetrandrine (2 pmol/mouse) markedly suppressed the tumor-promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 pg) in mouse skin initiated with 7,12-dimethylbenz[a]anthracene (50 pg), at a grade corresponding to that of another bisbenzylisoquinoline alkaloid, cepharanthine [197]. 

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