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Biomedical subjects

D G Kaufman

Publications and source records attributed to D G Kaufman.

At least 109 records · Page 6Linked to original sources
PubMed1980

Predominance of early endometrial cancers after long-term estrogen use.

Clinical stage and pathological characteristics of endometrial cancer cases were related to several aspects of estrogen prescribing. In comparing 256 cases with 321 community control subjects, estrogen use of less than 3 1/2 years' duration did not increase the risk of endometrial cancer for any stage, grade, histological type, or extent of ivasion. With long-term estrogen use (3 1/2 years or more), relative risks were significantly increased (5.2 to 7.6) for the early cancers--those clinically stage IA, histologically grade 1, and invading the endometrium only. These increases were seen with both high-dose (greater than 0.625 mg) and low-dose (less than or equal to 0.625 mg) preparations. Risks were only minimally increased for the more advanced cancers. However, long-duration estrogen use did produce an increased risk of advanced cancer when administration was continuous rather than cyclic.

Adenocarcinoma↗
PubMed1980

Induction of kidney tumours by a single dose of dimethylnitrosamine: dose response and influence of diet and benzo(a)pyrene pretreatment.

Seven days on a protein-free diet increases the susceptibility of rats to the action of DMN as a renal carcinogen. The dose response for the induction of kidney tumours by a single dose of dimethylnitrosamine (DMN) in these rats is reported. The first tumour was not found until 28 weeks after the dose. At 100 weeks the incidence ranged from 22.5% at the lowest dose (20 mg/kg) to 97% at the highest dose (60 mg/kg). The incidence in probits at any time between 50 and 100 weeks was linearly related to the log dose. Epithelial and mesenchymal tumours were produced in an approximate ratio of 2:1. The protein-free diet alters the rate of metabolism of DMN in the rat, and increases the alkylation of nucleic acids by this carcinogen in the kidney. Further treatment of the rat with benzo(a)pyrene can reverse, to some extent, the change in metabolism, but does not reverse the change in alkylation. It is shown that the change in kidney-tumour incidence produced by the change in diet, and by the treatment with benzo(a)pyrene, corresponds to the changes these treatments produce in the alkylation of kidney DNA by the carcinogen.

Animals↗
PubMed1980

Cycle-related toxicity and transformation in 10T1/2 cells treated with N-methyl-N'-nitro-N-nitrosoguanidine.

Exposure of C3H 10T1/2 Cl 8 cells, synchronized by release from confluence-induced arest of proliferation, to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 30 min at various points during the cell cycle causes dose-dependent toxicity (decrease in relative colony-forming efficiency or "survival") that increases linearly during the first G1 phase, reaches a maximum in early to middle S phase, and decreases during late S. In the course of the second S phase, toxicity again becomes maximal. The transformation rate (type III foci) increases and decreases with a similar pattern, increasing during the first G1 phase to a maximum during early S phase, subsequently decreasing, and then increasing again during the second S phase. Although periods of maximal toxicity and transformation roughly coincide with some portion of the S phase, the mechanisms underlying these phenomena appear to differ for the following reasons: (a) toxicity is linearly related to dose of MNNG, whereas the latter is linearly related to the logarithm of transformation rate, and (b) the ratio between toxicity and transformation varies with the cycle phase and the dose of MNNG.

Animals↗
PubMed1980

"Alternative" controls in a case-control study of endometrial cancer and exogenous estrogen.

To address the issue of detection bias among endometrial cancer cases and controls, women admitted to the North Carolina Memorial Hospital for dilatation and curettage (D&C) during 1970-1976 were selected as one of three control groups in a study of endometrial cancer and exogenous estrogen. Study subjects included 256 cases, 316 D&C controls, 224 gynecology controls and 321 community controls. The D&C controls had a higher frequency of estrogen use than either of the other control groups or the cases. These differences existed for both blacks and whites. When white cases were compared to either gynecology or community controls, relative risks were increased for long duration estrogen use and for recent use prior to diagnosis. With D&C controls, relative risks were not significantly different from unity irrespective of duration or recency of estrogen use. Exclusion of hyperplasias from the D&C controls had no substantive effect of these results. Bleeding was a presenting complaint for 92% of cases, 82% of D&C controls and 22% of gynecology controls. Both among cases and gynecology controls, there was no statistically significant association between bleeding and estrogen use, whereas this association was evident among D&C controls, and specifically among those who did not have pathologic evidence of endometrial hyperplasia. These data support the presence of detection bias among D&C controls but they do not provide evidence of this bias among endometrial cancer cases.

Aged↗
PubMed1978

Differing effects of isoleucine deficiency on the toxicity of MNNG for 10T1/2 and CHO cells.

Isoleucine deficiency sensitizes C3H 10T1/2 cells to the cytotoxic effects of MNNG. Synchrony of proliferation is not required for this effect since it occurs prior to full growth arrest and subsequent establishment of synchronous proliferation after refeeding in complete medium. Furthermore, confluence arrest of proliferation of 10T1/2 cells does not affect their cytotoxic response to MNNG, although they proliferate synchronously after replating at low density. In contrast, the toxicity of MNNG for CHO cells is not altered by isoleucine deficiency, even though these cells are readily synchronized by refeeding in complete medium after transient isoleucine deficiency.

Cell Count↗
PubMed1978

In vitro assay of cytotoxicity with cultured liver: accomplishments and possibilities.

Tissue cultures offer potential advantages for assaying the toxicity of chemicals and for evaluating tissue susceptibility to toxic agents. Several properties of cultured cells hinder the immediate, widespread use of tissue cultures to assay toxicity routinely. These points are illustrated by briefly reviewing attempts to utilize different types of hepatic cultures to evaluate the actions of carcinogenic chemicals in vitro. Hepatocytes in vivo apparently can metabolize all known procarcinogenic chemicals, but the process of tissue isolation and the environmental conditions in vitro may modify drastically the responses of hepatocytes and other cultured hepatic cells to toxic chemicals. Before cell cultures can be used routinely as the basis of screening systems to detect chemical toxins, specificity and sensitivity of response to chemicals representing all chemical classes must be validated by laboratory studies.

Animals↗
PubMed1977

Effect of systemic administration of BCG cell walls on bronchogenic carcinoma in hamsters.

Systemic injection of BCG cell walls was evaluated for effects on the development of respiratory tract tumors induced by intratracheal instillation of benzo[a]pyrene plus Fe2O3 in Syrian hamsters. Only 74% of animals developed respiratory tract tumors at the dose level of benzo[a]pyrene used. Treatment with BCG cell walls reduced the incidence of respiratory tract tumors to 50%. A similar effect of treatment with BCG cell walls was found when only malignant tumors of the respiratory tract were considered. Both single and multiple injections of BCG cell walls effectively reduced the incidence of respiratory tract tumors.

Animals↗
PubMed1976

Biochemical studies of isolated hamster tracheal epithelium.

The epithelial lining of respiratory air passageways is a primary target tissue for toxicity and carcinogenesis in man and in animal models of human disease. The importance of this target tissue was the basis for development of methods to study its biochemistry, and with this information to distinguish the unique properties of this tissue from properties common to all cell types. Biochemical methods employed labeling of macromolecules in isolated hamster treacheas during brief (less than 4 hr) incubation in vitro. Studies of RNA metabolism in isolated tracheas demonstrated a pattern of maturation of ribosomal RNA like that shown for other cell types. Alterations in RNA metabolism were observed in isolated tracheas obtained from vitamin A-deficient hamsters and hamsters previously treated by intratracheal administration of benzo[a]pyrene (BP) plus ferric oxide (Fe2O3) in vivo. Studies with toyocamycin, actinomycin D, and alpha-amanitin, all inhibitors of RNA metabolism, were performed to characterize the class of RNA molecules with a decreased proportion of labeling in tracheas from vitamin A deficient hamsters. In another series of experiments, BP was shown to bind to DNA in epithelial cells of isolated tracheas. The quantity of BP binding was increased by prior intratracheal treatment of hamsters with BP plus Fe2O3 in vivo, this induced binding was inhibited by addition of 7,8-benzoflavone to the incubation medium. Increased BP binding was also observed in isolated tracheas from hamsters believed to be in states of increased susceptibility to respiratory carcinogenesis in vivo. The results show that biochemical studies are feasible with this tissue. Furthermore, a number of questions of importance with regard to this target epithelium are best studied directly in its constituent cells.

Adenosine↗