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.

Development of a System for Controlled Release of Benzo(a)pyrene, 7,12-Dimethylbenz(a)anthracene, and Phorbol Ester for Tumor Induction in Heterotopic Tracheal Grafts

Abstract: The utility of the tracheal transplant model as a tool in in vivo carcinogenesis studies depends largely on the development of a good drug delivery system affording reproducible, sustained carcinogen release. Previously used methods have proven to be less than satisfactory. We studied the release of benzo( a )pyrene, 7,12-dimethylbenz( a )anthracene, and 12- O -tetradecanoylphorbol-13-acetate from pellets of varying composition. In vitro release of the two polycyclic hydrocarbons (PCH) from beeswax pellets showed little variability, regardless of PCH concentration. In marked contrast, in vivo release was highly variable, particularly at high PCH concentrations. This suggested that the in vivo variability was largely due to the toxic alterations of tissues, caused by carcinogen released at high rates. Pellets composed of beeswax:cholesterol in ratios of 1:1 to 1:9 showed markedly reduced rates of PCH release. At a ratio of 1:9, the overall release rate of benzo( a )pyrene was ∼1 µg/day compared to ∼7 µg/day for pellets with a pure beeswax matrix [100 µg benzo( a )pyrene pellets]. The variability of PCH release was simultaneously diminished, supporting the suspicion that it was a result of toxic tissue changes. Similarly reduced release rates could be obtained by adsorbing the PCH to charcoal particles. Studies with the promotor 12- O -tetradecanoylphorbol-13-acetate showed a release rate of 1.6 µg/day from pure beeswax (100 µg 12- O -tetradecanoylphorbol-13-acetate per pellet). This rate may have to be diminished before promotion studies in the tracheal transplant model can be attempted. Our studies demonstrate that protracted PCH release from pellets can be achieved by using a beeswax: cholesterol matrix instead of a pure beeswax matrix or by adsorbing the PCH to charcoal particles. Such pellets release at fairly constant rates, with little pellet-to-pellet variability. Thus, the major problem of using the tracheal transplant model for quantitative tumor induction studies with PCH9s appears to be resolved.

Effects of Insulin, Prolactin, Progesterone, and Estradiol on DNA Synthesis in Organ Culture of 7,12-Dimethylbenz(a) anthracene-induced Rat Mammary Tumors

Abstract: Summary The effect of various hormones or hormone combinations on DNA synthesis was investigated in organ cultures of 20 dimethylbenz(a)anthracene-induced rat mammary tumors. Three tumors were insulin independent and were totally insensitive to all other hormones tested. Seventeen tumors were insulin dependent for DNA synthesis and, in the presence of insulin, displayed variable responses to the other hormones. Nine of 12 such tumors were significantly stimulated by the combination of prolactin and progesterone. Given alone, these hormones were effective in only 25% of the tumors tested. Estradiol used at 2 dose levels, 0.001 or 1.0 µg/ml, acted in a reverse manner to progesterone and proved inhibitory in combination with prolactin in 40% of cases. It was ineffective alone except in 1 of 10 cases in which a stimulatory effect was recorded. A comparison in 4 tumors between estimation of DNA synthesis ([3H]thymidine incorporation into DNA) and colchicine-blocked mitoses demonstrated a good concordance. These results are discussed in terms of variations in the degree of hormone responsiveness of individual tumors and of the known hormone-dependent properties of the 7,12-dimethylbenz(a)-anthracene tumors in vivo.

Effect of Moderate Vitamin A Supplementation and Lack of Dietary Vitamin A on the Development of Mammary Tumors in Female Rats Treated with Low Carcinogenic Dose Levels of 7,12-Dimethylbenz(a)anthracene

Abstract: We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12-dimethylbenz( a )anthracene. The number of mammary tumors was significantly ( P < 0.05) reduced if prior to and during initiation with 7,12-dimethylbenz( a )anthracene the rats were fed a moderately increased (30 µg/day) or marginal (3 µg/day) amount of vitamin A, compared to rats fed an adequate (10 µg/day) amount of vitamin A. The number of mammary tumors was also significantly ( P < 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly ( P < 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum -fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant ( P < 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 µg/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 µg/day) intake of vitamin A, that resulted in a small, but statistically significant ( P < 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors. These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development.