Exposure of experimental animals to toxaphene induces hepatic cytochrome P-450 (CYP). Although chronic administration of toxaphene to mice was found to cause an increased incidence of liver tumors, a mechanism for its carcinogenicity has yet to be elucidated. We investigated two potential mechanisms of toxaphene-induced carcinogenicity: peroxisomal proliferation and DNA binding. Peroxisomal proliferation was evaluated by measuring the level of immunodetectable CYP 4A1, an isozyme of CYP that is specifically induced by peroxisomal proliferators, in hepatic microsomes from CD1 mice that were treated by oral gavage for seven consecutive days with corn oil vehicle or 10, 25, 50 or 100 mg kg(-1) toxaphene. In comparison to control mice, toxaphene-treated mice had increased liver weight, increased liver/body weight ratios and increased levels of total hepatic CYP and cytochrome b5. No increase in the level of immunodetectable levels of CYP 4A1 was found in hepatic microsomes from toxaphene-treated mice when compared to controls. In contrast, increases in immunodetectable CYP 4A1 were detected in hepatic microsomes from mice treated with the peroxisomal proliferator clofibrate. These findings suggest that toxaphene-induced induction of CYP may not involve CYP 4A1 and that peroxisomal proliferation may not be involved in toxicity. Significant increases in immunodetectable levels of CYP 2B were, however, detected in toxaphene-treated mice, and are consistent with earlier reports demonstrating that toxaphene, like many other pesticides, induces the phenobarbital-inducible subfamily of CYP. Analysis of DNA adduct levels in the livers of toxaphene-treated mice by DNA 32P-post-labeling showed no evidence of DNA adduct formation.

Animals↗

PubMedDate not supplied

The use of traditional toxicologic data in assessing neurobehavioral dysfunction.

In the United States, the regulation and testing of chemicals that may impact on human health is mandated by a number of different laws and regulated by several government agencies. Toxicologic screening in laboratory animals has created a major database for predicting adverse health effects of drugs, food and cosmetic ingredients, and manufactured chemicals. Test protocols and reporting requirements frequently differ between government agencies within the United States and between nations. Until recently, the emphasis for this required testing has been to identify those chemicals that may result in cancer or birth defects with little or no emphasis placed on neurobehavioral testing. The so-called "traditional toxicologic screen" presently includes acute, subchronic, chronic, teratology, and reproductive multispecies testing. The report for each segment of the test screen contains a myriad of data elements that have been observed by numerous technicians in the testing laboratory. These laboratory tests vary from general animal observations of animal body weight and food consumption to tests for hematology, blood chemistry, urinalysis, and histopathology. In addition, specialized tests may include other physiological measurements, neurologic tests, eye exams as well as functional testing to evaluate performance (e.g., open field, swimming maze, and T-maze). Reliability, quality control, and the difficulty in converting technician observation into quantifiable data elements that are free from bias is a primary concern for all testing laboratories. This paper focuses on the neurotoxicologic and behavioral information that can be gleaned from traditional toxicologic screens, the collection of study data, the effect of model selection, and the environmental considerations that may affect study outcome. The paper includes examples of compounds previously reported in the literature.

Animals↗

PubMedDate not supplied

Psychological impact on house staff of an initial versus subsequent emergency medicine rotation.

The objective of this study was to assess the psychological impact of a 4-week emergency medicine (EM) rotation on residents undergoing their first EM experience. These findings were compared to the psychological impact the rotation had on residents with prior EM experience. Data were obtained from a post hoc analysis of a previous study. Prerotation and postrotation psychological distress levels were assessed over a 4-week EM rotation. Anxiety and depressive symptoms were evaluated by the Brief Symptom Inventory and the Dissociative Experience Scale that together comprise a total of 14 psychometric scales. All scales were given at the beginning and end of the initial EM rotation for the academic year of 1994-1995. All information was coded and confidential. Eighteen junior residents (9/18 EM [50%]) were analyzed as a group and compared to 53 residents (34/51 EM [66%]) with prior exposure to the authors' emergency department. Residents doing their first EM rotation (N = 18) showed improvement in 13 of 14 scales (P = .002). Of the 13 scales that improved, 3 improved significantly: Brief Symptom Inventory = anxiety (P = .002) and Dissociative Experience Scale = absorption (P = .001) and other (P = .001). Residents with prior EM experience (N = 53) displayed worsening in 9 of 13 scales (P = not significant) and no change in 1. Residents undergoing their first EM rotation showed a significant decrease in psychological distress over the 4-week period. Residents with prior EM experience did not show a similar change.

Adult↗

PubMedDate not supplied

AIDS in South Africa.

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AIDS Serodiagnosis↗

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Postmenopausal HRT--a role for a safe antioestrogen.

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Animals↗