Commonalities in the structural determinants of toxicity in fish and mammals.
The CASE program, an expert structure-activity relational system, was used to identify the structural determinants associated with inhibition of the human isozyme P4502D, toxicity of cultured murine Balb 3T3 cells, induction of alpha 2u-globulin-associated nephropathy in male rats, systemic toxicity in mice and rats, and acute toxicity in minnows. Comparison of the structural determinants thus identified revealed a significant mechanistic overlap between the determinants of cellular toxicity and systemic toxicity in mice, rats, and minnows.
Rosenkranz
H S
HS
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261.
Matthews
E J
EJ
Klopman
G
G
D016475:3T3 Cells; D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D003530:Cyprinidae; D065607:Cytochrome P-450 Enzyme Inhibitors; D005103:Expert Systems; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D014116:Toxicology / Q000379:methods*
D000510:Alpha-Globulins; D065607:Cytochrome P-450 Enzyme Inhibitors; C013803:alpha 2u globulin