COMPARISON OF THE HEPATIC AND RENAL EFFECTS OF 1,4-DICHLOROBENZENE INTHE RAT AND MOUSE

The effects of 1,4-dichlorobenzene (DCB) have been compared in male F3 44 rats given 0 (corn oil control), 25, 75, 150, and 300 mg/kg DCB and male B6C3F(1) mice given 0 (corn oil control), 300, and 600 mg/kg DCB by daily oral gavage five days per week for 1, 4, and 13 weeks. The t wo highest rat and both mouse dose levels were the same as those emplo yed in a NTP bioassay, where DCB produced kidney tumors in male rats a nd liver tumors in mice. DCB produced significant dose-related increas es in relative liver weight in both the rat and the mouse which was as sociated with, respectively, mild and marked centrilobular hypertrophy . Administration of DCB also produced a sustained induction of microso mal cytochrome P450 content and 7-pentoxyresorufin O-depentylase activ ity in both species. Western immunoblotting studies demonstrated that DCB induced CYP2B isoenzyme(s) in both rat and mouse liver microsomes. Replicative DNA synthesis was studied by implanting osmotic pumps con taining 5-bromo-2'-deoxyuridine in study Weeks 0-1, 3-4, and 12-13. In the rat hepatocyte labeling index values were only increased in anima ls given 300 mg/kg DCB for 1 week, whereas hepatocyte labeling index v alues were significantly increased in mice given 300 and 600 mg/kg DCB for 1 and 4 weeks. DCB treatment produced significant increases in ra t renal P-1/P-2 proximal tubule cell labeling index values at all time points, whereas little effect was observed in mouse kidney. The obser ved species difference in DCB-induced liver tumor formation may reflec t the greater sensitivity of the mouse to tumor promotion by a CYP2B i nducer. For the kidney, the present data provides further evidence tha t while DCB-induced alpha(2U)-globulin nephropathy is associated with a sustained stimulation of cell replication in male rat renal proximal tubule cells, this effect is not observed in the male mouse. (C) 1997 Society of Toxicology.