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Biomedical subjects

D K Gulati

Publications and source records attributed to D K Gulati.

35 records · Page 2Linked to original sources
PubMed1989

Reproductive toxicity of 2,2-bis(bromomethyl)-1,3-propanediol in a continuous breeding protocol in Swiss (CD-1) mice.

The effect of 2,2-bis(bromomethyl)-1,3-propanediol (BMP) on reproduction in Swiss CD-1 mice was evaluated by use of a continuous breeding protocol. BMP was administered in the feed at 0.1, 0.2, and 0.4% concentrations. Both male and female F0 mice (20 pairs per treatment group, 40 pairs of control animals) were dosed 7 days prior to and during a 98-day cohabitation period. Although the fertility index was unchanged in the high-dose group, BMP exposure significantly decreased the numbers of litters per pair, pups born alive per litter, and pup weight when adjusted for litter size. Crossover mating between treated and control F0 animals indicated a specific effect only on female reproductive capacity. At the highest dose, BMP caused a body weight decrease in the F0 animals of both sexes with no effect on relative organ weights. Sperm concentration, motility, morphology, and estrual cyclicity were unaffected by BMP exposure. Histopathology in the F0 animals revealed specific kidney lesions in both sexes; males were more sensitive than females. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated to nonsiblings of the same treatment group. The effect of high-dose BMP exposure on F1 fertility, body and organ weights, sperm parameters, and estrual cyclicity was the same as that for the F0 animals, with the exception of the lack of renal lesions seen in the F1 females. These data show that BMP impaired fertility in female mice in both generations in the absence of an effect on reproductive organ weights and estrual cyclicity.

Animals↗
PubMed1989

Results and evaluations of 48 continuous breeding reproduction studies conducted in mice.

Results of 48 continuous breeding reproduction (RACB) studies are summarized and control data from these studies are used to determine the statistical sensitivity of each endpoint from different parts of these studies. Results of testing individual chemicals compared well with results of multigeneration studies reported in the literature. Continuous breeding studies were able to discriminate reproductive toxicants from nontoxicants, and provided valuable structure-activity information. When mice in continuous cohabitation produce multiple litters, the statistical sensitivity of fertility endpoints is quite high and is comparable to that associated with other sensitive indicators of reproductive function, such as testis weight and sperm parameter measures. The principal advantages of the RACB protocol in comparison to multigeneration studies are: (1) the increased sensitivity and statistical power, (2) the ability to monitor progression of toxicity and to detect subfertility, (3) use of a battery of endpoints including sperm measures, (4) the ability to determine the affected sex(es), and (5) slightly reduced testing time.

Animals↗
PubMed1988

Interlaboratory studies with the Chinese hamster V79 cell metabolic cooperation assay to detect tumor-promoting agents.

Three laboratories participated in an interlaboratory study to evaluate the usefulness of the Chinese hamster V79 cell metabolic cooperation assay to predict the tumor-promoting activity of selected chemicals. Twenty-three chemicals of different chemical structures (phorbol esters, barbiturates, phenols, artificial sweeteners, alkanes, and peroxides) were chosen for testing based on in vivo promotion activities, as reported in the literature. Assay protocols and materials were standardized, and the chemicals were coded to facilitate unbiased evaluation. A chemical was tested only once in each laboratory, with one of the three laboratories testing only 15 out of 23 chemicals. Dunnett's test was used for statistical analysis, and differences between treated- and control-cell responses were analyzed at P less than or equal to .01. Chemicals were scored as positive (at least two concentration levels statistically different than control), equivocal (only one concentration statistically different), or negative. For 15 chemicals tested in all three laboratories, there was complete agreement among the laboratories for nine chemicals. For the 23 chemicals tested in only two laboratories, there was agreement on 16 chemicals. With the exception of the peroxides and alkanes, the metabolic cooperation data were in general agreement with in vivo data. However, an overall evaluation of the V79 cell system for predicting in vivo promotion activity was difficult because of the organ specificity of certain chemicals and/or the limited number of adequately tested nonpromoting chemicals.

Animals↗
PubMed1988

Reproductive effects of theophylline in mice and rats.

Theophylline was administered by gavage in 13-week studies to B6C3F1 mice (0, 75, 150, 300 mg/kg/day) and F344 rats (0, 37.5, 75, 150 mg/kg/day) with significant reductions in male mouse terminal body and testicular weights. Male rats also displayed reduced testicular weight, as well as nonsignificant but dose-related decreases in body weight. There was a significant but non-dose-related decrease in female mouse body weight. In parallel studies of B6C3F1 mice and F344 rats, theophylline administered in the diet (0, 0.1, 0.2, 0.4%) produced significantly decreased terminal body weights in male and female mice, but not rats. In rats, cauda epididymis weight was reduced at the high dose compared to the control group, and there was an increase in abnormal sperm. These studies were followed by continuous breeding reproductive assays in CD-1 mice in which theophylline was administered in feed (0.0, 0.075, 0.15, and 0.30%; calculated doses of 0, 125, 265, and 530 mg/kg/day, respectively) to breeding pairs for 14 weeks. There was a dose-dependent decrease in the number of live pups produced per litter, a significant decrease in the number of litters produced per pair (0.30%) and in the adjusted live pup weight (0.30%), a decrease in the percentage of pups born alive (0.15 and 0.30%), and an increase in the number of days needed to produce each litter (0.30%). After 19 weeks of continuous treatment at 0.30%, a crossover mating trial indicated that females and males were adversely affected by theophylline, as judged by the decreased percentage of pups born alive, the decreased live pup weight, and the decreased number of live pups per litter relative to matings within the control group, but the effects in females were more extensive. Based on other studies, there is a suggestion that the observed changes in fertility may be partially attributed to embryotoxicity.

Animals↗
PubMed1985

Reproductive and developmental toxicity of ethylene glycol in the mouse.

The effects of ethylene glycol on reproduction of CD-1 mice were tested in a protocol which permitted continuous breeding during a specified interval. The dosage amounts of 0, 0.25, 0.5, or 1% ethylene glycol by continuous administration in drinking water for male and female mice were selected from the general toxic responses observed in a 14-day pilot study. After the first week of administration, begun at 11 weeks of age, the animals were housed one male and one female per cage for 14 weeks during which time any offspring were examined, sexed, weighted, and killed to allow continuous mating of the first generation. At the end of the 14-week cohabitation period, the males and females were separated and any litters delivered after that time were kept until weaning. Those second-generation animals were mated at about 70 days of age. Slight, but statistically significant, decreases were found in the numbers of litters per fertile pair and live pups per litter in the 1% dose group and live pup weight at the 1% dose groups compared to control F0 mice. Facial anomalies were noted in a number of offspring of high-dose-treated mice and an examination for skeletal defects demonstrated a pattern including reduction in the size of bones in the skull, fused ribs, and abnormally shaped sternebrae and vertebrae in the high-dose-treated, but not the untreated, mice. Neither the 0.25 nor 0.5% dose groups were significantly affected. No clinical signs of toxicity or significant adverse effects on body weight or water consumption were seen at the doses used, but two deaths occurred at the 0.5% quantity which may have been related to oxalate crystal deposition in the kidney.

Animals↗
PubMed1984

Sister-chromatid exchanges and chromosome aberrations in lymphocytes from monkeys exposed to ethylene oxide and propylene oxide by inhalation.

The ability of long-term exposures to inhaled ethylene oxide (EO) and propylene oxide (PO) to induce sister-chromatid exchanges (SCEs) and chromosome aberrations in peripheral lymphocytes of monkeys was investigated. Five groups of adult male cynomolgus monkeys were exposed at 0 (shared control), 50, or 100 ppm EO, and at 100 or 300 ppm PO (7 hr/day, 5 days/week) for 2 years. EO exposures at 50 and 100 ppm resulted in statistically significant increases in sister-chromatid exchange rates and in the incidence of chromosome aberrations in monkey lymphocytes. Both EO-exposed groups had increased numbers of SCEs/metaphase compared to controls, with the SCEs/metaphase of the EO 100 ppm group also significantly elevated versus the EO 50 ppm group. Variability of SCEs/metaphase within each monkey increased even more than the increase in total SCEs/metaphase group with increasing EO exposure. Chromatid-type aberrations were also significantly increased for both EO 50 and EO 100 ppm groups compared to controls. Statistically significant increases in the number of chromosome-type aberrations (excluding gaps) were found only in the EO 100 ppm group. Combined chromatid- and chromosome-type aberrations were increased in both EO 50 and EO 100 ppm groups. No group differences in the number of gaps were found. In lymphocytes from monkeys exposed at 100 and 300 ppm PO, there were no group differences compared to controls for any variable-chromatid or chromosome-type aberrations, gaps, or SCEs/metaphase. These results indicate that EO is a more potent clastogen than PO and demonstrate, for the first time, statistically significant effects of EO on both SCEs and chromosome aberrations in lymphocytes of nonhuman primates.

Animals↗
PubMed1984

Reproductive toxicity of ethylene glycol monoethyl ether tested by continuous breeding of CD-1 mice.

The reproductive toxicity of ethylene glycol monoethyl ether (EGEE) was evaluated in the Fertility Assessment by Continuous Breeding protocol. Both male and female CD-1 mice were given 0, 0.5, 1.0 or 2% EGEE in the drinking water and were housed as breeding pairs continuously for 14 weeks. Significant adverse effects on fertility were seen at 1 and 2% but not at 0.5%. After the continuous breeding phase of this test was completed, treated males were housed with control females and treated females with control males and fertility and reproduction were compared to the corresponding pairs of control male and control female mice. Both males and females from the 1 and 2% groups were affected. Testicular atrophy, decreased sperm motility and increased abnormal sperm were noted in the treated males, but no specific anomalies were detected in the females.

Abnormalities, Drug-Induced↗
PubMed1982

Effect of diesel exhaust emissions, particulates, and extract on sister chromatid exchange in transplacentally exposed fetal hamster liver.

The genotoxic activity of diesel exhaust emissions, particulate matter, and an organic extract of the particulate matter was evaluated in transplacentally exposed Syrian hamster fetal liver cells. The frequency of sister chromatid exchange (SCE) was determined on day 13 of gestation. The extract of diesel particulate matter caused a dose-dependent increase in the frequency of SCE with a doubling in the incidence above 320mg/kg. The diesel particulate matter and diesel exhaust emissions did not alter the frequency of SCE. The extract and particulate matter did cause a dose-dependent decrease in the mitotic activity of the fetal liver. The in utero SCE analysis was demonstrated to be a sensitive assay for determination of the genotoxic activity of a complex mixture in transplacentally exposed fetuses.

Animals↗
PubMed1976

Additive and Synergistic Growth-inhibiting Properties of the Canaline-Urea Cycle Amino Acids.

Growth studies with Lemna minor revealed the additive and synergistic growth-inhibiting properties of the canaline-urea cycle amino acids. Simultaneous canavanine and canaline treatment caused an additive reduction in frond production. Ureidohomoserine interacted with canaline or canavanine to affect synergistically L. minor growth by enhancing individual canavanine or canaline toxicity and increasing the additive growth reduction caused by canavanine plus canaline. The ornithineurea cycle amino acids effectively counteracted both the additive and synergistic growth-inhibiting properties of the canaline-urea cycle compounds.

Journal Article↗
PubMed1975

Cytological studies on onion root-tip cells treated with water-soluble extract of tobacco smoke condensate from commercial cigarettes.

The effect of water-soluble extract of tobacco smoke condensate (TSC) from two commercially available cigarettes with dirrerent types of filters was studied on the cytology of root-tip cells of onion (Allium cepa). One of the cigarettes had a 2-cm cellulose acetate filter, and the other had a filter comprised of 1 cm of cellulose acetate and 2 cm of activated charcoal. TSC from these cigarettes induced mitotic abnormalities. To investigate whether these two commercial filters could retain cigarette smoke component (s) responsible for mitotic irregularities, the cigarettes were defiltered, and TSC was prepared and tested on the young roots of onion. Observations revealed that the cytological effect of TSC from defiltered cigarettes was not significantly different from the effect of TSC from cigarettes with filters. Thus, the filters utilized in these cigarettes do not retain compound(s) responsible for mitotic irregularities in the root-tip cells of onion. With increasing concentrations (0.01% ot 0.1%) of TSC from cigarettes with filters and defiltered, precent mitotic abnormalities increased. These abnormalities included scattering, stickiness, lagging, condensation, and breaking of chromosomes during metaphase. Bridging and lagging of chromosomes were observed during anaphase.

Chromosomes↗
PubMed1975

Studies on the Growth Effects of the Canaline-Urea Cycle Amino Acids with Lemna minor L.

The aquatic microphyte, Lemna minor L., was utilized to assess the relative toxicity and general growth effects of canavanine, canaline, ureidohomoserine (UHS), and canavaninosuccinate (CSA). These amino acids are constituents of the canaline-urea cycle and structural analogues of the ornithine-urea cycle amino acids.Comparative growth studies with L. minor revealed that the canaline-urea cycle amino acids are potent antimetabolites. With the exception of CSA, they are extremely toxic at a concentration of 5 mum. Over a concentration range of 1 to 4 mum, canavanine is the most growth-inhibiting of the canaline-urea cycle amino acids. At or above 5 mum, canavanine and canaline possess comparable toxicity. UHS is less growth-inhibiting than canavanine or canaline, and CSA is the least toxic of the canaline-urea cycle intermediates.

Journal Article↗
PubMedDate not supplied

Comparison of single-, double- or triple-exposure protocols for the rodent bone marrow/peripheral blood micronucleus assay using 4-aminobiphenyl and treosulphan.

Two human carcinogens, 4-aminobiphenyl (4AB) and treosulphan (Treo), were tested in male B6C3F1 mice for the induction of micronuclei in bone marrow and peripheral blood cells by 1-, 2- and 3-exposure protocols. Both compounds tested positive. The magnitude of response with respect to the incidence of micronucleated polychromatic erythrocytes by 2- and 3-exposure protocols was considerably higher than by the single-exposure protocol. The peripheral blood results for Treo were as typically seen with a 24-h delay when compared to the bone marrow. The peripheral blood results for 4AB, however, differed from those expected. The incidence of MN-PCE in peripheral blood of animals exposed to 4AB was significantly greater than seen in the bone marrow in 2- and 3-exposure protocols. There was also an increase in the % PCE at the 60 mg/kg dose level as a function of time. Based on these studies, it is concluded that a step-wise scoring scheme may be the best protocol for rodent micronucleus assay, involving a 3-exposure protocol with single sampling of bone marrow (24 h after the last treatment) and two samplings of peripheral blood (24 h and 48 h after the first treatment). This approach is cost-effective, it limits the number of animals required and provides maximum sensitivity.

Aminobiphenyl Compounds↗