Search PubMed⌕ Search

Biomedical subjects

D K Sinha

Publications and source records attributed to D K Sinha.

29 records · Page 2Linked to original sources
PubMed1982

Effect of estrogen and progesterone on cellular replication of human breast tumors.

A total of 54 infiltrating carcinomas of the breast were studied for estrogen receptor concentration in the tumor cytosol and thymidine-labeling indexes. The results showed that there was no significant difference in the level of thymidine-labeling index between 22 primary and 32 metastatic breast cancers. No significant association between the levels of thymidine-labeling index and the presence or absence of estrogen receptors was observed. The effect of "physiological" doses of estrogen and progesterone on cell proliferative activity was studied by the level of thymidine-labeling indexes in the tumor cells in 10 patients with multiple skin and s.c. metastases. Tumor biopsies were performed for labeling indexes both before and after hormonal treatment. The results showed that physiological doses of estrogen and progesterone induced a significant rise in thymidine-labeling index within 3 days after hormonal treatment in seven of the 10 tumors. Of the seven tumors that showed a rise in thymidine-labeling index, three were estrogen receptor positive and four were estrogen receptor negative. Of the three nonresponsive tumors, one was estrogen receptor positive and two were estrogen receptor negative. The study suggests that estrogen and progesterone can induce cell replication in both estrogen receptor-positive and -negative tumors.

Adult↗
PubMed1981

Tumorigenesis of mammary gland by 7,12-dimethylbenz(a)anthracene during pregnancy: relationship with DNA synthesis.

The relationship between mammary cell proliferation during pregnancy and susceptibility to 7,12-dimethylbenz(a)anthracene (DMBA) was examined. DMBA was administered intravenously to Sprague-Dawley rats on the 5th, 10th or 15th day of pregnancy. [3H]thymidine labelling index (LI) of the mammary cells at the time of treatment with the carcinogen was determined and found to be higher in the pregnant rats than in age-matched virgin controls. In spite of the high proliferative index of the mammary cells, significant inhibition of tumorigenesis occurred in the pregnancy rats allowed to complete pregnancy and parturition following treatment with DMBA. However, when pregnancy was terminated by cesarian section shortly after treatment with DMBA, there was a significantly higher tumor incidence as compared to the "full-term" rats. It was observed that the earlier the pregnancy was terminated, the greater was the incidence of mammary tumors. This would indicate that the inhibitory effect of pregnancy is related to changes occurring during the later half of gestation. The differentiation of mammary cells for milk synthesis as pregnancy progresses is postulated to be a major reason for the observed refractoriness of the mammary cells to DMBA at that time.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Growth of mammary glands from monodispersed cells and susceptibility to 7,12-dimethylbenz[alpha]anthracene.

Monodispersed mammary cells inoculated into the subscapular fat pad of isologous female rats developed into full-formed ductal mammary glands. The growth pattern of these outgrowths followed that of normal mammary gland, as indicated by labeling index (LI). Tumorigenesis in these outgrowths induced by 7,12-dimethylbenz[alpha]anthracene (DMBA) was in direct proportion to the level of LI. A similar correlation of tumorigenesis and LI was also observed in the mammary gland of virgin female rats. Our data show that application of this technique in the study of mammary cell physiology and carcinogenesis would be very useful.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Enhancement of mammary tumorigenesis by dietary selenium deficiency in rats with a high polyunsaturated fat intake.

The effect of selenium depletion on mammary tumorigenesis following dimethylbenz[a]anthracene administration was examined in female Sprague-Dawley rats that were fed different levels and types of fats. Four basal diets deficient in selenium were used: (a) 1% corn oil; (b) 5% corn oil; (c) 25% corn oil; and (d) a high saturated fat diet containing 1% corn oil and 24% hydrogenated coconut oil. The comparable selenium-adequate diets were obtained by adding 0.1 ppm of selenium to each of the basal diets. In animals that received an adequate supplement of selenium, an increase in fat intake was accompanied by an increased tumor incidence when corn oil was used in the diets. A high saturated fat ration, on the other hand, was much less effective in this respect. Only in those rats that were maintained on a high polyunsaturated fat diet (25% corn oil) did selenium depletion result in a further increase in tumor incidence and tumor yield. Such an augmentation was not observed in animals given either a 1 or a 5% corn oil ration or a diet rich in saturated fat. Regardless of selenium status, almost all of the tumors found were adenocarcinomas. An enhancement of tumorigenesis as a result of selenium deficiency in rats fed the 1% corn oil regimen was detected provided a high dose of dimethylbenz[a]anthracene was used, suggesting that alterations in dimethylbenz[a]anthracene metabolism might be involved under this condition. The antioxidant property of selenium is discussed as a possible mechanism by which selenium protects against tumorigenesis, especially in animals with a high polyunsaturated fat intake.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Induction of mammary tumors in aging rats by 7,12-dimethylbenz[a]anthracene: role of DNA synthesis during carcinogenesis.

Two routes of administration were used to test the susceptibility of the mammary gland of the rat to 7,12-dimethylbenz[a]anthracene (DMBA) carcinogenesis in relation to age of the tissue. In one series of experiments, 60-, 70-, 90-, 120-, 150-, and 200-day-old female noninbred Sprague-Dawley rats were given DMBA iv. In parallel experiments, rats of the same ages as those above were given DMBA by local application. Mammary tumors developed in 80-90% of the 60- and 70-day-old rats and in 40% of the 90-day-old rats. Rats 120 days old and older were completely "refractory" to DMBA. In contrast, all rats, irrespective of their ages, developed tumors when DMBA was applied locally. The DNA synthesis labeling index (LI) of mammary glands of rats in two series of experiments was examined by [3H]thymidine incorporation and autoradiography at 24, 48, and 72 hours after DMBA treatment. DMBA, given iv significantly inhibited DNA synthesis in mammary glands, but DMBA applied locally significantly increased the LI of the mammary glands. Thus the LI of the mammary glands in 60-day-old rats increased from 8% (control, untreated) to 16% (rats receiving local applications of DMBA), whereas the LI of the mammary glands in 150-day-old rats increased from 1.15% (control, untreated) to 8% (rats receiving local application of DMBA).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Estrogenic properties of 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene in rats.

Previously, the 3,9-dihydroxy derivative of benz[a]-anthracene was shown to be weakly estrogenic. The availability of the related diol of the mammary carcinogen dimethylbenz[a]-anthracene, i.e., 3,9-dihydroxy-7,12-dimethylbenz[a]anthracene (3,9-diOHDMBA), prompted a similar study of its estrogenic properties. The competitive binding studies of 3,9-diOHDMBA with 17beta-estradiol in the uterine cytosol of immature SD rats gave a Ka of 1.7 x 10(8) M-1. 17beta-Estradiol (10(-9) M) binding to the 8S binding protein was inhibited by 3,9-diOHDMBA at concentrations similar to those of nafoxidine HCl (1 x 10(-5) M). Bioassay demonstrated that the diol possesses 1/4,464 the activity of 17beta-estradiol.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Comparative chromosome study of normal mammary tissue, carcinogen-induced mammary tumors, and hyperplastic alveolar nodules in the rat: Brief communication.

The chromosome constituents of 101 normal mammary gland cells, 122 hyperplastic alveolar nodule (HAN) cells, and 360 cells from eleven 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in the WF rat were examined. Both mammary gland and HAN had normal diploid karyotype patterns, whereas mammary tumors showed frequent (approximately 30%) abnormalities, e.g., aneuploidy, pseudodiploidy, polyploidy, and structural aberrations such as breakage and translocation. These results suggested that chromosome constituents of HAN cells are essentially the same as those of the normal mammary epithelial cells.

Animals↗
PubMed1976

Estrogenic properties of 3,9-dihydroxybenz[a]anthracene, a potential metabolite of benz[a]anthracene.

The estrogen receptor binding properties of 3,9-dihydroxybenz[a]anthracene (3,9-diOHBA) were determined in uterine cytosol of immature Sprague-Dawley rats by competitive binding experiments with [3H]estradiol and sucrose density centrifugation. 3,9-DiOHBA inhibited estradiol binding to the 8S binding protein at a concentration (1.2 X 10(-5) M) approximately equal to that of nafoxidine-HCl (3 X 10(-5) M) required to inhibit estradiol-specific binding, and bioassay for estrogenic activity substantiated this finding.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

In vivo antitumor activity of tetrahydrobenz(a)anthraquinone derivatives.

Female rats bearing DMBA induced mammary carcinomas were treated with a new anthraquinone derivative related to mitoxantrone. The drug was administered at a dose of 5 mg/kg daily for 10 days. Tumor regression was noted in 78% of the animals with growth rate reduced from +74.91% to -12.60%. The results demonstrate that replacement of a polar hydroxy group of mitoxantrone with a nonpolar hydrocarbon moiety does not impair its antitumor activity and in fact may influence its availability to endocrine systems.

Animals↗