Showing papers on "7,12-Dimethylbenz[a]anthracene published in 1969"

Mammary cancer induction by 7,12-dimethylbenz(a)anthracene: relation to age.

Abstract: Mammary glands were transplanted from donors treated with 7,12-dimethylbenz(a)anthracene to untreated isologous recipients. Incidence of mammary tumors in mammary grafts from 56-day-old donors was significantly higher than that in grafts from 120-day-old donors, regardless of the age of the recipient hosts. Whent mammary glands were transplanted from untreated donors to isologous recipients that subsequently received 7,12-dimethyl-benz(a)anthracene, a similar difference in tumor incidence in the grafts was observed. In contrast to mammary glands of older females, mammary glands of young adult female rats are highly vulnerable to the carcinogenic effect of 7,12-dimethylbenz(a)anthracene.

Isolation and degradation of DNA from cells treated with tritium-labeled 7,12-dimethylbenz(a)anthracene: studies on the nature of the binding of this carcinogen to DNA.

Abstract: In an attempt to obtain a source of material for chemical studies, the binding of 7,12-dimethylbenz(a)anthracene (DMBA) was studied in E. coli, B. subtilis , and ascites tumor cells. For the bacteria a dose-dependent binding was found, but the level of binding was low. In the case of the ascites tumor cells in the mouse, binding of DMBA to DNA, RNA, and protein showed a dependence on time after injection of the hydrocarbon, but again the level of binding was much less than that found earlier for mouse skin. Mouse L-cells and chicken fibroblasts in tissue culture again gave a low level of DMBA binding, but rodent embryo cells in culture, as reported earlier, were a good source of DNA having bound DMBA. Enzymic degradation of this material and subsequent fractionation suggested that the DMBA was bound to the bases of DNA, resulting in partial inhibition of the enzymic degradation of the DNA. A similar partial inhibition was observed for DNA alkylated with half-sulphur mustard but not for methylated DNA. The low level of in vivo , binding obtained suggests that alternative methods will be needed to establish both the nature of the bound hydrocarbon moiety and the base at which it is attached.

Prevention by spironolactone of 7,12-dimethylbenz(a)anthracene-induced adrenal necrosis.

Abstract: SummaryAdministration of spironolactone protects the rat against 7,12-dimethylbenz (a) anthracene-induced adrenal necrosis.

Effect of age and sex on the development of neoplasms in wistar rats receiving a single intragastric instillation of 7,12‐dimethylbenz(a)anthracene

Abstract: Wistar rats of different age and sex received a single intragastric instillation of 7,12-dimethylbenz(a)anthracene (DMBA). During the following 16 months, 136 of 284 rats developed 182 tumors, of which half were malignant. Among 98 untreated controls, 8 rats developed tumors, of which 4 were malignant. Among the youngest groups (8–15 days) exposed to DMBA, fibroadenoma of the breast in females and subcutaneous sarcoma in both sexes were the most frequent. Among young adult females (6–8 weeks), mammary carcinoma predominated; older females (26 weeks) had less breast tumors. Among adult males, epidermoid carcinoma and papilloma of the skin were most frequent. Castration suppressed development of breast cancer.

Biochemical Characteristics of Mammary Glands and Mammary Tumors of Rats Induced by 3-Methylcholanthrene and 7,12-Dimethylbenz(a)anthracene

Abstract: Summary Nucleic acids, lipids, and several enzyme activities were measured in mammary carcinomas induced in rats by 3-methylcholanthrene (MCA) or 7,12-dimethylbenz(a)anthracene (DMBA) These biochemical parameters in the neoplasms were also studied after ovariectomy of, or the administration of either estrogen or androgen to, the tumor-bearing animals In untreated tumor-bearing animals, the levels of triglycerides and the activities of glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase were similar in MCA- and DMBA-induced tumors arising after multiple feeding of the carcinogen, but these parameters were significantly different in tumors arising after a single intubation of DMBA Ovariectomy produced decreases of similar magnitude in several enzyme activities in both types of carcinogen-induced carcinomas, and treatment with androgen or estrogen caused changes in the biochemistry of these tumors that only in part resembled the effects observed after ovariectomy Treatment with estrogen produced a secretory response in the DMBA-induced carcinomas, and this response was accompanied by marked elevations in malate dehydrogenase and α-glycerolphosphate dehydrogenase activities, along with a 9-fold increase in triglyceride levels No such secretory response was observed in MCA-induced neoplasms The activities of several enzymes in the mammary glands from animals bearing DMBA-induced neoplasms were significantly reduced compared to mammary glands from control animals devoid of tumors or mammary glands of animals bearing MCA-induced neoplasms Thus, subtle biochemical differences were found in mammary carcinomas induced by single or multiple doses of DMBA, and these biochemical differences may be related to differences in growth rate and responsiveness

Influence of Hypothalamic Lesions on the Induction and Growth of Mammary Cancers in Sprague-Dawley Rats Receiving 7,12-Dimethylbenz(a)anthracene

Abstract: Lesions of the median eminence of the tuber cinereum of the hypothalamus inhibit the induction of mammary cancer in Sprague-Dawley female rats that subsequently receive intragastric 7,12-dimethylbenz(a)anthracene. In contrast, such lesions significantly accelerate the growth of established mammary cancer and cancel the inhibiting effect of ovariectomy.

The effects of schedule and dose of 7,12-dimethylbenz(a)-anthracene on the induction and growth of mammary carcinomas in Sprague-Dawley female rats.

Abstract: The induction and subsequent growth of mammary carcinomas in female Sprague-Dawley rats is significantly enhanced by dividing oral exposures to 7,12-dimethylbenz(a)anthracene into 5 weekly doses, and it is slightly depressed by 5 doses given every other day, as compared with single doses.

Comparative Biologic Activities of 7,12-Dimethylbenz(a)anthracene, 7-Hydroxymethyl-12-methylbenz(a)anthracene, 7,12-Dihydroxy-methylbenz(a)anthracene, and 4-Methoxy-7,12-dimethylbenz(a)anthracene in the Sprague-Dawley Female Rat

Abstract: 7,12-Dimethylbenz(a)anthracene (DMBA) and the 7-hydroxy-, 7,12-dihydroxy-, and 4-methoxy- derivatives were studied in parallel to determine their effects on the hemopoietic system, adrenal cortex, liver enzymic activity, and body weight in Sprague-Dawley female rats. The monohydroxy compound caused more extensive damage to hemopoietic and adrenocortical tissue than DMBA, whereas the 7,12-dihydroxy- and 4-methoxy- derivatives were inactive. Liver menadione reductase and N -2-fluorenylacetamide hydroxylase activities were stimulated by DMBA and 4-methoxy-DMBA, but not significantly by the hydroxymethyl compounds. Mean body weight was not influenced by 4-methoxy-DMBA or 7,12-dihydroxy-DMBA. DMBA induced a temporary loss of body weight, whereas 7-hydroxy-DMBA caused a significant and prolonged loss. These observations strongly support the conclusion that DMBA-induced hemopoietic and adrenocortical damage is due to its metabolite, 7-hydroxy-DMBA.

Genetic Determination of Differential Inflammatory Reactivity and Subcutaneous Tumor Susceptibility of AKR/J and C57BL/6J Mice to 7,12-Dimethylbenz[a] anthracene

Abstract: Summary Since previous work has shown that 7,12-dimethylbenz[a]-anthracene (DMBA) causes less inflammation in AKR/J than in C57BL/6J mice, the genetic nature of this differential inflammatory response was investigated. The criterion for high reactivity was the formation of ulcers after skin application of DMBA. F 1 hybrids were slightly less high reacting than the C57BL/6J mice. Of the F 2 , 72% were high reacting. The back-cross of F 1 hybrids to C57BL/6J produced only high reactors, but to AKR/J high- and low-reacting mice. Mating of low-reacting F 1 backcross mice to C57BL/6J mice yielded 100%, and to AKR/J 0%, high reactors. Backcross of low-reacting F 2 mice to C57BL/6J gave 100%, and to AKR/J 0%, high-reacting mice. Backcross of high-reacting F 1 backcross and F 2 mice to C57BL/6J yielded only high-reacting, and to AKR/J high- and low-reacting, mice. These findings suggest that the low inflammatory response of the AKR/J mice is controlled by a single incompletely recessive factor. Results with DBA/2J mice, their F 1 hybrids, and backcrosses of these F 1 hybrids to AKR/J, also indicated inheritance by a single autosomal genetic factor. The higher inflammatory reactivity of the C57BL/6J mice was accompanied by higher susceptibility to subcutaneous tumor induction by DMBA. Furthermore, results with mice differing only in inflammatory reactivity showed that inflammatory reactivity and susceptibility to s.c. tumor induction are inherited together and are probably directly related.

Influence of germ-free status on hepatoma induction by 7,12-dimethylbenz(a)anthracene in C3H mice.

Abstract: THE susceptibility of C3H male mice to the apparently spontaneous development of hepatomas has long been recognized1. Castration reduces the incidence of these tumours2 and a high protein diet increases it3.

The induction of malignant lymphomas and other tumors by 7,12-dimethylbenz(a)anthracene in the Syrian golden hamster.

Abstract: Summary Single and four weekly repeated intravenous injections of 7,12-dimethylbenz(a)anthracene (DMBA) in 15% fat emulsion were given to adult Syrian golden hamsters. The single DMBA treatment resulted in the induction of malignant lymphomas with an incidence of 30% in females and 25% in males, while repeated DMBA injections gave rise to incidences of 18% in females and 7% in males. In controls the corresponding figures were 2% in females and 7% in males. In addition, a number of other types of tumors were observed in the treated and control animals. Of the twenty-five malignant lymphomas found in the treated groups, 6 were the stem-cell (undifferentiated) type, with an average latent period of 34 weeks, 8 were the lymphocytic type, with an average latent period of 46 weeks, and 11 were the histiocytic type with an average latent period of 69 weeks. Histologically, stem-cell and lymphocytic types of malignant lymphomas were nonthymic, involving the lymph nodes, spleen, liver, kidneys, and occasionally the bone marrow; the appearance of malignant lymphomas of the histiocytic types in treated as well as in controls was similar to those described in an earlier study. The first experimental induction of malignant lymphomas in the hamster with chemical carcinogen provides a model that more closely resembles anatomically the human disease than the other previously reported rodent lymphomas.

Thyroiditis in Buffalo strain rats ingesting 7,12-dimethylbenz(a)anthracene.

Abstract: Bei mannlichen und weiblichen Ratten des Buffalo-Stammes trat nach Verabreichung von 7,12-Dimethylbenzanthracen eine Thyroiditis auf.

Protection of cultured hamster embryonic cells from 7,12-dimethylbenz(a)anthracene cytotoxicity and the induced synthesis of aryl hydroxylase.

Abstract: Treatment of secondary cultures of hamster embryonic cells with an excess of thymidine (5mm) caused an inhibition of DNA synthesis which was reversible. This treatment permitted a study of the effects of polycyclic hydrocarbons on cells inhibited at the G1-S boundary and on cells entering the S phase of the cell cycle. Cytotoxic damage caused by 7,12-dimethylbenz(a)anthracene (DMBA) treatment of cells after their release from thymidine inhibition was prevented by the simultaneous exposure to an equimolar concentration of benz(a)anthracene (BA) (4 µ m). The DMBA depression of the rate of DNA synthesis and the inhibition of cell division were also prevented by simultaneous BA treatment. These results suggest that protection from DMBA cytotoxicity may be due to a BA induction of aryl hydroxylase which may have degraded the DMBA to less toxic metabolites. DNA synthesis was shown not to be required for induction of aryl hydroxylase; in fact, an equal amount of the enzyme activity was induced during either synthesis or inhibition of DNA. Cultures induced simultaneously with BA + DMBA synthesized a higher level of aryl hydroxylase than cultures with either BA or DMBA.

Progesterone metabolism by adrenal homogenates of rats treated with 7, 12-dimethylbenz [A] anthracene.

Abstract: [4-14C]-progesterone has been incubated with adrenal homogenates prepared from rats which had been administered the carcinogen, 7,12-dimethylbenz[a]-anthracene. The production of corticosterone was reduced markedly in preparations from treated animals when compared to untreated control animals. During the second week following treatment, an increased synthesis of corticosterone and other adrenal cortical steroids becomes evident. The relationship between adrenal cortical pathology, circulating plasma corticosterone levels and impairment of biosynthetic hydroxylating enzyme systems following administration of the carcinogen is discussed.

The Effects of 7,12-Dimethylbenz(a)anthracene on the Ovarian Response of Mice and Rats to Gonadotrophins

Abstract: Administration by stomach tube of 7,12-dimethylbenz(a)anthracene (DMBA) (30 mg/100 gm body weight) in oil caused a decrease in the ovarian weights of C57BL/6J, C3D2F1, CAF1, B6AF1, B6D2F1, and C57BL/6J × C3HeB/FeJ mice, but it did not affect the ovarian weights of C3HeB/FeJ × NZY mice or of Sprague-Dawley or Fischer rats. DMBA treatment also eliminated the ovarian weight gain, which normally is seen 48 hours after chorionic gonadotrophin (CG) injection, in C57 mice 34 days of age or less, but there was no significant effect on the action of CG in stimulating ovarian weight gain in C57 mice 56 days of age or more. In C3D2F1 mice, the ovarian weight response was eliminated up to 23 days of age, but in older mice of this strain the inhibition was not complete and was more variable in degree. The ovarian weight response to CG was reduced within 3 days of DMBA treatment in mature B6D2F1 or immature B6AF1 mice, and within 7 days in mature CAF1 mice. However, the carcinogen had no significant effect on ovarian weight stimulation by CG in mature B6AF1, C57BL/6J × C3HeB/FeJ, or C3HeB/FeJ × NZY mice. In a less extensive series of experiments, substitution of pregnant mare serum (PMS) as the gonadotrophin after DMBA treatment gave results parallel to those obtained with CG. Ovarian weight gain following PMS was inhibited in immature Sprague-Dawley rats, but not in Fischer rats at any of the 3 weights studied. Uterine weight was lower in most DMBA-treated immature mice and Sprague-Dawley rats than in the controls and increased less following gonadotrophin injection. In the majority of mature mice and rats, however, uterine weights did not differ significantly between DMBA-treated and control animals either before or after gonadotrophin injection. Amounts of DMBA in arachis oil equivalent to or less than 20 mg/100 gm administered through a stomach tube or 2 mg/100 gm injected intraperitoneally were ineffective in inhibiting the action of gonadotrophins on the ovaries of immature C57BL/6J mice. The number of viable ovarian follicles was greatly reduced in mice within 3 days after DMBA treatment, and there were none present 100 days afterwards. There was no obvious toxic effect of DMBA on the rat ovaries. Carcinogen treatment was followed by a loss of total body weight in some, but not all, rats and mice. There was no absolute correlation between the inhibition of ovarian response to gonadotrophin and the decrease in total body weight following treatment with the carcinogen. An interpretation of the results is given in terms of the action of DMBA on pituitary secretion in both mice and rats, and in terms of direct action on ovarian follicles in mice only.