Toxicity of ortho-substituted bromobenzenes to isolated hepatocytes: comparison to in vivo results.
In this study, freshly prepared isolated rat hepatocytes were exposed to various concentrations of bromobenzene and six ortho-substituted bromobenzenes. Toxicity was estimated by trypan blue dye exclusion and release of GPT and K+ over a 0- to 4-hr time course. In all cases a close correlation among these three indices was observed. The rate of response depended on the exposure level and the nature of the o-substituent. The relative toxicity followed the order C2H5 greater than CH3 greater than or equal to CF3 greater than Br much greater than H greater than OCH3 much greater than CN. This order does not correlate well with the in vivo toxicity data previously obtained in this laboratory (Toranzo E. G., Gillesse, T., Mendenhall, M., Traiger, G.J., Riley, P.G., Hanzlik, R.P., and Wiley, R.A. (1977). Toxicol. Appl. Pharmacol. 40, 415-425.); in fact an almost inverse relationship is indicated. Several possible reasons are proposed in order to rationalize the discrepancy between these two results. The results emphasize the need for caution when using isolated hepatocytes to screen new compounds for purposes of determining their potential in vivo toxicity, at least until the differences between hepatocytes in vivo and hepatocytes in vitro are more thoroughly understood.
D000818:Animals; D001969:Bromobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013997:Time Factors
D001969:Bromobenzenes