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Biomedical subjects

M T Moslen

Publications and source records attributed to M T Moslen.

65 records · Page 4Linked to original sources
PubMed1975

Vinyl chloride-induced deactivation of cytochrome P-450 and other components of the liver mixed function oxidase system: an in vivo study.

Liver microsomal enzyme activities were measured 24 hr after a 6 hr exposure to 5% vinyl chloride in male rats pretreated with phenobarbital, Aroclor 1254 or the control vehicle. Liver injury as indicated by serum transaminase elevations after vinyl chloride, was found only in phenobarbital and Aroclor 1254 animals while cytochrome P-450 contents and oxidative N-demethylation of aminoantipyrine and ethylmorphine were markedly decreased in all groups. Glucose-6-phosphatase, cytochrome b5 and NADPH and NADH cytochrome P-450 reductase were scarcely affected. This selective enzymatic deactivation is consistent with a cytochrome P-450 centered activation of vinyl chloride to a reactive electrophile.

Alanine Transaminase↗
PubMed1975

Hepatotoxicity of vinyl chloride and 1,1-dichloroethylene. Role of mixed function oxidase system.

Vinyl chloride, an occupational carcinogen, produces acute liver injury in rats pretreated with phenobarbital or Aroclor 1254. Injury appears related to morphologic changes in the endoplasmic reticulum. The degree of injury, as indicated by elevation of serum enzymes derived from the liver, correlates with the magnitude of induction of cytochrome P-450 and its reduction by NADPH. Hepatic injury following 1,1-dichloroethylene exposure differs strikingly from that caused by vinyl chloride and appears to involve plasma membranes, mitochondria, and chromatin and spares endoplasmic reticulum. Induction of cytochrome P-450 appears to protect against 1,1-dichloroethylene but not vinyl chloride.

Animals↗
PubMedDate not supplied

Advantages of a combined testing protocol (CTP) with multiple endpoints: the reverse tier approach.

A multi-endpoint CTP approach provides an efficient procedure to investigate the hazards of chemicals in our environment. Genotoxicity to multiple tissues is assessed after an exposure of limited duration by using a variety of sensitive short-term tests. Resources are thus conserved and results obtained without long delays. Additional information helpful in understanding the observed genotoxic effects is readily obtained in the same experiment by inclusion of additional nongenotoxic endpoints. Numbers of animals required to test chemicals are substantially decreased by increasing the amount of information obtained from each animal. Flexibility is a basic asset of a CTP approach. Therefore, pharmacokinetics of the test chemical or mixture and concerns about subpopulations of exposed humans can guide all aspects of the design of CTP protocol including the animal species, the exposure protocol and the endpoints. The procedures selected for evaluating potential mutagens should be based primarily on the usefulness of the information generated and secondarily on the cost and resources required to perform the procedure. The most expensive procedure is that procedure which does not generate useful information, regardless of the initial cost. The CTP as presently discussed is an attempt to maximize useful information in the most efficient manner possible. Although considerably more expensive than in vitro procedures, the protocol is far less expensive than conducting individual short-term animal procedures, and a fraction of the cost and time required to perform a typical cancer bioassay. Chemicals that are of major concern, for example as in the case of extensive human exposure, would be a prime candidate for initial testing by this methodology.

Animals↗
PubMedDate not supplied

Two cannula method for parenteral infusion and serial blood sampling in the freely moving rat.

Materials and techniques are described for positioning and exteriorizing two chronic venous cannulas in the rat. A cannula for fluid infusion is placed in the inferior vena cava via the femoral vein and exteriorized on the tail, whereas a cannula for blood withdrawal is placed in the superior vena cava and exteriorized in the scapular region. Grooming behavior and range of motion are not impeded since the cannula used for chronic infusion is shielded by a light-weight tail cover instead of a torso harness. Application of this method can minimize numbers of rats used in total parenteral nutrition (TPN) studies as demonstrated by our feasibility study in which serum parameters of liver function were serially monitored in toxin-treated rats infused with nutrient mixtures.

Animals↗