Species differences in the toxicity of p-chloro-o-toluidine to rats and mice. Covalent binding to hepatic macromolecules and hepatic non-parenchymal cell DNA and an investigation of effects upon the incorporation of [3H] thymidine into capillary endothelial cells.
The interaction of p-[14C] chloro-o-toluidine with hepatic macromolecules of rats and mice has been investigated. At all time points after single administration the extent of binding decreased in the order protein greater than RNA greater than DNA in both species. The level of binding to mouse liver DNA was greater than that to rat liver DNA after both single and repeated administration. In vitro studies showed that mouse liver fractions catalysed the binding of p-chloro-o-toluidine to calf thymus DNA more readily than rat liver fractions. Conversely, binding to protein and RNA was more marked in the rat than in the mouse. Species differences in DNA repair rates were not observed. The results failed to demonstrate a preferential persistence of binding to mouse liver nonparenchymal cell DNA. Autoradiographic determinations did not demonstrate any effect of p-chloro-o-toluidine upon the incorporation of [3H] thymidine into subcutaneous capillary endothelial cells. The results suggest that different reactive metabolites are responsible for binding to DNA and protein, and that the pattern of reactive metabolites formed from p-chloro-o-toluidine in the mouse differs from that formed in rats.
Bentley
P
P
Bieri
F
F
Muecke
W
W
Waechter
F
F
Stäubli
W
W
D000818:Animals; D001665:Binding Sites; D002196:Capillaries / Q000378:metabolism; D002417:Cattle; D004247:DNA / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland; D014052:Toluidines / Q000378:metabolism* / Q000633:toxicity
D014052:Toluidines; C556393:p-chloro-o-toluidine hydrochloride; D012313:RNA; D004247:DNA; D013936:Thymidine