Differential protooncogene expression in Sprague Dawley and Fischer 344 rats during 1,2-dichlorobenzene-induced hepatocellular regeneration.
Significant differences in hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) have been reported (Gunawardhana, L., Sipes, I.G., 1991. Dichlorobenzene hepatotoxicity strain differences and structure activity relationships. Adv. Exp. Med. Biol. 283, 731-734; Stine, E.R., Gunawardhana, L., Sipes, I.G., 1991. The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer 344 and Sprague-Dawley rats: isomer specific and strain-specific differential toxicity. Toxicol. Appl. Pharmacol. 109, 472-481; Valentovic, M.A., Ball, J. G., Anestis, D., Madan E., 1993a. Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats. J. Appl. Toxicol. 13, 1-7; Kulkarni, S.G., Duong, H., Gomila, R., Mehendale, H.M., 1996. Strain differences in tissue repair response to 1,2-dichlorobenzene. Arch. Toxicol. 70, 714-723. Kulkarni, S.G., Warbritton, A., Bucci, T., Mehendale, H.M., 1997. Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats. Toxicology. 120, 79-88). Although, hepatotoxic injury of o-DCB is greater in Fischer 344 (F344) when compared with Sprague Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality (Kulkarni et al., 1996; Kulkarni et al., 1997, see these refs. above). However, the mechanism(s) for this interstrain difference in tissue repair is (are) not currently understood. The objectives of the present study were (1) to investigate if the differences in compensatory tissue repair are reflected in differential protooncogene expression in S-D versus F344 rat livers and (2) to investigate if changes in protooncogene expression could explain the decrease and delay in tissue repair response beyond a threshold of 0.6 ml o-DCB/kg. Male S-D and F344 rats (8/9 weeks old) were administered either 0.6 or 1.2 ml o-DCB/kg and changes in expression of protooncogenes c-myc (immediate early) and Ha-ras (delayed early) were examined over a time course. Findings of this study indicate that the timing and extent of c-myc and Ha-ras expression varies in the two strains following administration of o-DCB. Thus, the timing and extent of compensatory liver regeneration that ensues following o-DCB administration in S-D and F344 rats is temporally concordant with the protooncogene expression in the two strains.
Kulkarni
S G
SG
Division of Toxicology and Louisiana Institute of Toxicology, College of Pharmacy and Health Sciences, University of Louisiana at Monroe, 71209-0470, USA.
Harris
A J
AJ
Casciano
D A
DA
Mehendale
H M
HM
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002722:Chlorobenzenes / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D011905:Genes, ras / Q000187:drug effects / Q000235:genetics; D015151:Immunoblotting; D017403:In Situ Hybridization; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D011519:Proto-Oncogenes / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D002722:Chlorobenzenes; C004726:2-dichlorobenzene