Biomedical subjects

D L Greenman

Publications and source records attributed to D L Greenman.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Nonneoplastic changes induced in female C3H mice by chronic exposure to diethylstilbestrol or 17 beta-estradiol.

The long-term nonneoplastic effects of estrogenic diets were studied in female C3H/HeJ and C3HeB/FeJ mice. C3H/HeJ mice received diets containing 0, 10, 100, or 500 ppb diethylstilbestrol (DES) or 100, 1000, or 5000 ppb 17 beta-estradiol (E2) from 6 to 110 wk of age. C3HeB/FeJ females were fed diets containing nominal concentrations of 0, 10, 100, or 500 ppb DES from 6 to 136 wk of age. Responses of both strains to DES were qualitatively identical. Histological changes in the reproductive tract induced or increased by DES in both strains and by E2 in C3H/HeJ mice included stromal mucoid changes in the vagina and cervix, epithelial keratinization in the vagina, and glandular hyperplasia in the uterine horns. Increasing doses above 10 ppb DES or 100 ppb E2 increased the prevalence and, in some cases, severity of these responses. Dose-responses to DES for these endpoints were virtually indistinguishable in the two strains. At 10 ppb DES or 100 ppb E2 there were minimal or no observable effects. When the nonneoplastic dose-response data were compared with neoplastic dose-response data previously reported, no consistent relation between doses causing neoplastic and nonneoplastic responses was seen for the two estrogens.

Animals↗

PubMedDate not supplied

Cause-of-death assignment at the National Center for Toxicological Research.

The system for assigning cause of death in animal studies of carcinogenicity at the National Center for Toxicological Research (NCTR) is described. An empirical study of the NCTR's experience with its current cause-of-death assignment system based on selected representative experiments is reported. Issues investigated include the degree of confidence associated with histologic cause-of-death assignment, potential age-, dose-, and sex-related differences in assigned grades of certainty of cause of death, and frequencies of identification of various organ-specific and systemic diagnoses as the cause of death. Implications for age-adjusted statistical tests of carcinogenicity that require cause-of-death data are discussed.

Animals↗

PubMedDate not supplied

Oral squamous cell carcinoma in ad libitum-fed and food-restricted Brown-Norway rats.

A high incidence of oral squamous cell carcinoma was present in male and female Brown-Norway rats fed ad libitum or food-restricted dietary formulations. One hundred eight-nine rats were examined from 4 dietary treatment groups: male ad libitum, male food-restricted, female ad libitum, and female food-restricted. The ad libitum treatment groups for both males and females had significantly more cases of oral squamous cell carcinoma than cohort food-restricted groups. In ad libitum rats, 10 of 47 (21%) males and 15 of 47 (32%) females had oral squamous cell carcinoma, whereas only 4 of 47 (9%) males and 5 of 48 (10%) females in the food-restricted groups were similarly affected. The food-restricted rats lived significantly longer than ad libitum cohorts, so the higher incidence of squamous cell carcinoma was not dependent on extended lifespans. In addition to the dietary influence, a significant difference in oral squamous cell carcinoma incidence occurred between various familial lines. Family lines having representatives in both ad libitum and food-restricted groups had lower oral squamous cell carcinoma incidences in the food-restricted group whether comparing affected litters or individuals. Results suggest that the incidence of oral squamous cell carcinoma in our colony of Brown-Norway rats can be influenced by both the dietary treatment group and genetic predilection within certain pedigrees.

Animal Feed↗

PubMedDate not supplied

The histochemical and ultrastructural characterization of hyaline material in the endometrium of mice fed diethylstilbestrol.

Histochemistry and electron microscopy were used to examine hyaline material within the endometrium of mice continuously fed diethylstilbestrol (DES). Virgin female mice were fed diets containing 0, 320 or 640 ppb DES from 4 weeks of age. All animals reported on in this study were sacrificed when moribund and ranged from 622 to 762 days of age. Irregular deposits of hyaline material were seen throughout the connective tissue stroma with frequent accumulations seen immediately beneath the surface epithelial membrane and around blood vessels. The material was characterized by a paucity of cells and fibrous material but exhibited an eosinophilic reaction and was PAS-positive. Histochemistry indicated collagen was present even though electron microscopy revealed a homogeneous, amorphous structure virtually devoid of a fibrous component. Numerous plasma cells were seen in close proximity to macrophages and lymphocytes. This material was probably a product of collagen degradation and a subsequent immune response elicited in the endometrium.

Administration, Oral↗

PubMedDate not supplied

Influence of a purified diet and route of administration on the metabolism and disposition of estradiol in B6C3F1 mice.

The metabolism and disposition of [6,7-3H]estradiol ([3H]E2) given by gavage (po) or intravenously (iv) were examined in female B6C3F1 mice fed either the purified AIN-76A (AIN) or cereal-based NIH-07 (NIH) diet for a period of 8 weeks prior to treatment with E2. Initially, 40.6 Ci of [3H]E2 was given iv to each mouse. Subsequently, 45.6 Ci of [3H]E2 was given po to the same mice. Samples of blood, urine, and feces were obtained during a 48-hr period after each dosing. Total radioactivity was determined for each sample. Urine and plasma samples were analyzed by HPLC, and the radiolabeled metabolites were tentatively identified and quantified. Statistical comparisons were made of the effects of diet, route of administration, and interactions among groups. Analysis revealed: 1) greater fecal than urinary excretion of radioactivity regardless of route of administration or diet fed, 2) more radioactivity excreted in the urine of AIN-fed than in NIH-fed mice, significantly different only after iv administration (p less than 0.02), and 3) a greater feces:urine ratio of excreted radioactivity following iv than po administration and from NIH-than AIN-fed mice. Metabolite profiles showed: 1) no differences in urine due to route of administration, 2) estriol conjugates dominated urinary metabolites, 3) accumulation of radioactive material in plasma that apparently was tritiated water, with more rapid accumulation of tritiated water after po than iv administration, 4) relatively more plasma estradiol-17-glucuronide, estriol-3-sulfate, and estriol in po- than in iv-treated mice, 5) estradiol-3, 17-sulfate in plasma of iv- but not po-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMedDate not supplied

Urinary bladder neoplasms induced in BALB/c female mice with low doses of 2-acetylaminofluorene.

Large numbers of female BALB/c mice were exposed to low levels of 2-acetylaminofluorene (2-AAF) in the diet. The dose response for urinary bladder neoplasms exhibited a shallow trend to low doses which increased sharply at the higher doses. The dose response over the entire dosage range gave the impression of a "threshold" type response below the mid-doses. Since the tumor incidence at the lower doses was less than 1.0 percent, relatively few urinary bladder tumors occurred. Thus, it was deemed advisable to re-examine noninvasive or early invasive bladder carcinomas and to study the dose response for only the "unequivocal" urinary bladder tumors. Examination of the dose response curves for "unequivocal" urinary bladder tumors showed a positive trend over the low end of the dose range. As a further check, an analysis was conducted on only invasive or metastasizing bladder carcinomas. In this case, there was no significant low dose trend. Thus, the shape of the low dose response curve for bladder carcinomas remains uncertain.

2-Acetylaminofluorene↗