This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.

Animals↗

PubMed1985

Carbamoylation of glutathione reductase and changes in cellular and chromosome morphology in a rat cell line resistant to nitrogen mustards but collaterally sensitive to nitrosoureas.

A Walker 256 rat carcinoma cell line (WR) with acquired resistance to nitrogen mustards has been found to lack cross-resistance to nitrosoureas. Although total cellular glutathione pools were similar in the parent (WS) and resistant cell lines (WS, 2.5 X 10(-6); WR, 2.0 X 10(-6) mol/mg protein), glutathione reductase activity was 3.98 in WR compared to 8.67 nmol reduced nicotinamide adenine dinucleotide phosphate oxidized per microgram protein per min in WS cells. Treatment of cells with a carbamoylating nitrosourea, N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea, produced a dose-dependent inhibition of glutathione reductase and depletion of thiols in both cell lines. The drug caused no direct DNA strand breakage, but a differential mitotic spindle-chromosome stain showed that spindle formation was inhibited in WR cells at N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea concentrations of greater than 50 microM. In WS cells, mitotic figures were still visible at 100 microM. Chromosomal damage was expressed in both cell lines at concentrations of 25 microM. The number and extent of these aberrations were greater in WR than WS. Observed karyotypic abnormalities included polyploidy, chromosome decondensation, and endoreduplication. In interphase cells, transmission electron microscopy showed that the most prevalent drug-induced lesions included (a) disappearance of plasma membrane filopodia, (b) appearance of membrane blebbing, and (c) development of irregular crescent-shaped nuclei. These morphological and cytogenetic changes correlate with cytotoxic responses of these cell lines to N,N'-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea and would be consistent with drug-induced inhibition of glutathione reductase.

Animals↗

PubMed1977

Unusual presentation of an adrenal tumour.

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Adrenal Cortex Neoplasms↗

PubMedDate not supplied

Scientific journals and their authors' financial interests: a pilot study.

BACKGROUND: The credibility of modern science is grounded on the perception of the objectivity of its scientists, but that credibility can be undermined by financial conflicts of interest. The US Public Health Service and the National Science Foundation issued regulations effective October 1, 1995, regarding the disclosure of financial interests in the submission of grant proposals. Several scientific journals have also established pertinent policies for authors and editors. The objectives of this study were: (1) to select a set of published articles and observe the degree to which a sample of authors hold a financial interest in areas related to their research that are reportable under current standards, and (2) to examine the hypothesis that significant numbers of authors of articles in life science and biomedical journals have verifiable financial interests that might be important for journal editors and readers to know. This paper measures the frequency of selected financial interests held among lead authors of certain types of scientific publications and assesses disclosure practices of authors and journals. METHOD: These objectives were applied to a pilot study of Massachusetts academic scientists who were cited as first or last author in at least one article published in 1992 in 14 leading journals of cell or molecular biology and medicine. We created a database of every original article published in 1992 by 14 leading life science and biomedical journals, supplemented by data sets consisting of (1) Massachusetts biotechnology firms, including their officers and scientific advisory boards, and (2) scientists listed as inventors on patents or patent applications registered with the World Intellectual Property Organization. RESULTS: We examined 1,105 university authors (first and last cited) from Massachusetts institutions whose 789 articles, published in 1992, appeared in 14 scientific and medical journals. Authors are said to 'possess a financial interest' if they are listed as inventors in a patent or patent application closely related to their published work; serve on a scientific advisory board of a biotechnology company; or are officers, directors, or major shareholders (beneficial owner of 10% or more of stock issued) in a firm that has commercial interests related to their research. Applying the criteria to the reference population of journals and Massachusetts academic authors, we measured the following frequencies for lead authors: 0.20 for serving on a scientific advisory board; 0.07 for being an officer, director, or major shareholder in a biotechnology firm, and 0.22 for being listed as an inventor in a related patent or patent application. The joint frequency of articles in the journals reviewed with a lead author that meets one of the three conditions is 0.34. CONCLUSIONS: One of every three articles in our sample has at least one Massachusetts-based author with a financial interest, and 15% of the authors in our sample have a financial interest relevant to one of their publications. For the year 1992, the rate of published voluntary disclosures of financial interest (as defined in our study) is virtually zero, but relatively few scientific and biomedical journals at that time required any such disclosure to journal editors and reviewers. Further research is needed to determine the effectiveness of mandatory disclosure requirements by some journals.

Authorship↗

PubMedDate not supplied

Liquid chromatographic determination of zoalene in medicated feeds.

A rapid, reliable separation and quantitation of zoalene (3,5-dinitro-o-toluamide) from feeds is accomplished by using reverse phase liquid chromatography (LC) and ultraviolet detection. An extraction technique which is similar to the present AOAC official colorimetric method is used before chromatographic analysis. This extraction is followed by an activated alumina cleanup and LC to separate zoalene from feed matrix. The methodology was applied to a variety of spiked feed matrices, and yielded good recoveries. Liquid chromatographic results were shown to correlate with colorimetric determinations.

Animal Feed↗