Species differences in response to photohemolytic agents.
Species differences in red blood cell susceptibility to the photohemolytic agents chlorpromazine, menadione and tetracycline were examined in mouse, rat, dog, and human blood. Menadione and tetracycline (25 microM) hemolyzed mouse but not dog, rat, or human red blood cells (RBC) when irradiated with UV light but not in the dark. Chlorpromazine (25 microM) produced a photohemolytic response in all four species with mouse and rat RBC lysing fastest followed by human then dog cells. Investigations into the nature of these species differences suggested that the size of mouse RBC may contribute to its high sensitivity to photohemolytic agents. An investigation of the effect of UV light on key antioxidant enzymes revealed species differences in enzyme inactivation. These data suggest that mouse RBC may be particularly vulnerable to phototoxic agents, especially those compounds which produce active oxygen species and, therefore, may prove more useful than human RBC as a model for predicting phototoxic potential of some chemical entities.
Robertson
D G
DG
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Bailey
D L
DL
Martin
R A
RA
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016166:Free Radical Scavengers; D006461:Hemolysis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D010777:Photochemistry; D051381:Rats; D013045:Species Specificity; D013752:Tetracycline / Q000494:pharmacology; D014466:Ultraviolet Rays; D014812:Vitamin K / Q000494:pharmacology
D016166:Free Radical Scavengers; D014812:Vitamin K; D013752:Tetracycline; D002746:Chlorpromazine