Metabolic processes in isolated rat small intestine villus cells: effects of cis-diamminedichloroplatinum (II).
Intestinal cells were isolated from male Fischer 344 rats by the collagenase portal vein perfusion procedure and evaluated for direct effects of cis-diamminedichloroplatinum (CDDP) and ethylacrylate (EtAc) on metabolic activities. Specific activities of marker enzymes of intestinal crypt and villus cells indicated that the preparations contained predominantly villus cells. Cell viability was generally greater than 90%, and was maintained longest when the cells were suspended in M-199 medium supplemented with 1% BSA. EtAc, an industrial intermediate which is toxic to tissues which are directly exposed to this chemical, had no apparent effect on rates of glucose metabolism or protein synthesis in suspensions of the isolated intestinal cells. These metabolic processes, however, were inhibited by the anticancer agent, CDDP; the mechanism of cytotoxicity of CDDP may therefore be due to interference with intermediary metabolism. The present studies indicate that isolated intestinal cell suspensions may be useful in examining direct and immediate effects of chemicals which are toxic to the intestinal epithelium, and in evaluating potential cytotoxic effects of CDDP analogs which have been developed.
Kralovánszky
J
J
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Jenkins
W L
WL
Greenwell
A
A
Melnick
R L
RL
D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013393:Sucrase / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism
D000179:Acrylates; D009153:Mutagens; C040833:ethyl acrylate; D007770:L-Lactate Dehydrogenase; D013937:Thymidine Kinase; D000520:alpha-Glucosidases; D013393:Sucrase; D005947:Glucose; D002945:Cisplatin