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.

Activity of 6-Methyl-8-substituted Ergolines against the 7,12-Dimethylbenz[a]anthracene-induced Mammary Carcinoma

Abstract: Summary The ability of a series of 8β-carboxamido ergolines, 8-formamido ergolines, and 8-methyl ergolines to cause regressions of established dimethylbenz[a]anthracene-induced mammary carcinomas was compared to some ergot alkaloids. Although most of the ergoline derivatives depressed serum prolactin concentrations in rats, only a few had pronounced effects against the dimethylbenz[a]anthracene-induced mammary carcinoma in rats. Some derivatives from each of the three groups of substituted ergolines gave comparable activities against the dimethylbenz[a]anthracene-induced mammary carcinoma.

Role of Erythropoietin in 7,12-Dimethylbenz(a)anthracene Induction of Acute Chromosome Aberration and Leukemia in the Rat

Abstract: The incidence of chromosome aberrations in rat bone marrow, examined 6 hr after the administration of 7,12-dimethylbenz(a)anthracene, was significantly enhanced by induction of anemia 0-48 hr before the carcinogen treatment and was suppressed by induction of polycythemia. The suppressive influence of polycythemia was reversed by sheep erythropoietin injected shortly before or after the carcinogen injection; this suppressive effect was proportional to the dose of erythropoietin used. These data suggest that erythropoietin is essential to make bone-marrow cells susceptible to chromosome aberrations with 7,12-dimethylbenz(a)anthracene. The incidence of carcinogen-induced leukemia was also increased by anemia and suppressed by polycythemia induction.

Depression of Homograft Rejection and Graft- versus -Host Reactivity following 7,12-Dimethylbenz(a)anthracene Exposure in the Rat

Abstract: Summary An attempt to demonstrate a significant depression of cell-mediated immunity at the beginning of carcinogenesis by chemicals was made in the rat by skin homografts and graft- versus -host assays. A weak but highly significant prolongation of survival time was observed when F344 skin grafts were performed, across a weak (non- AgB ) histoincompatibility, in Lew rats 10 to 13 days after 7,12-dimethylbenz(a)anthracene treatment was started. The impairment of graft- versus -host reactivity of F344 spleen cells from donors given 7,12-dimethylbenz(a)anthracene 5 to 8 days before the assay was more evident when either weak (F344 × Lew F 1 ) or strong (F344 × Bf F 1 ) histocompatibility antigens were challenged. Further graft- versus -host assays with cells from the donor sensitized against the hybrid partner were performed in order to investigate the mechanism of cell-mediated immunity damage. There was no difference in sensitization lowering of 7,12-dimethylbenz(a)anthracene-treated animals whether the carcinogen was given before or after sensitization. This suggests that lymphocytic damage occurs in cell-mediated immunity depression, while this type of immunity does not show the early, remarkable damage characterizing the humoral processes.

Modification of the effect of a gonadoliberin analog on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by hormone replacement.

Abstract: A gonadoliberin analog, (d-leucyl 6 , desglycyl-NH 2 10 , prolyl ethylamide 9 ) gonadoliberin, is known to suppress ovarian function and plasma prolactin levels. Its antitumor activity was evaluated against mammary tumors induced in Sprague-Dawley rats by dimethylbenz(a)anthracene. Observations were made when the analog, referred to as A-43818, was given alone and together with estrogen replacement or perphenazine. A-43818, 10 µg s.c. twice a day for 6 weeks, was highly effective in producing tumor remissions. All of the 11 animals survived throughout the observation period, complete regressions occurred in 8 of 13 tumors, and 2 were classified as static. None of the 16 tumors in 12 control rats regressed, and there were 4 deaths. When estradiol benzoate, 2 µg s.c. each day, was administered with the A-43818, antitumor activity was suppressed; only 2 of 17 tumors regressed, 6 were static, and 5 of the 10 rats in this group died. Perphenazine, 1 mg i.m. daily, a dose known to cause hyperprolactinemia, also impaired the efficacy of A-43818. Three of 14 tumors regressed, 6 were static, and the rest continued to grow; 3 of the 12 rats died within 6 weeks of starting treatment.

Fluorescence spectra of nucleoside-hydrocarbon adducts formed in mouse skin treated with 7,12-dimethylbenz[a]anthracene.

Abstract: Hydrolysates of DNA that had been isolated from mouse skin treated with 3H-labelled 7,12-dimethylbenz[a]anthracene (DMBA) were subjected to chromatography on Sephadex LH20 columns and 3H-labelled products that eluted in the region expected for nucleoside-hydrocarbon adducts were purified further by high pressure liquid chromatography (h.p.l.c.). The fluorescence spectra of three major products that were resolved by this method were determined using photoncounting spectrophotofluorimetry. The fluorescence spectra of all three products were anthracene-like and similar to the spectra of nucleoside-hydrocarbon adducts obtained from DNA that was incubated with 3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz[a]anthracene 1,2-oxide (DMBA-3,4-diol 1,2-oxide). This is consistent with the idea that the metabolic activation of DMBA in mouse skin occurs through the formation of 'bayregion' diol-epoxides in the 1,2,3,4-ring.