Evaluation of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) following treatment of rats and mice with p-dichlorobenzene

p-Dichlorobenzene (PDCB) has been reported to produce tumors in the male an d female mouse liver and in the male rat kidney in 2-year gavage studies (N PT, 1987). To elucidate the possible mechanisms of carcinogenicity more ful ly, UDS and RDS were evaluated in B6C3F(1) mouse hepatocytes and F-344 rat kidney cells by autoradiography following in vivo administration of PDCB. A ll corn oil gavage doses of PDCB (300, 600, and 1,000 mg/kg) and the negati ve control resulted in <0 net grains/nucleus (NG) in the mouse liver and ra t kidney, indicating that PDCB does not induce UDS in either tissue. Compar ed to controls with less than or equal to 0.29% hepatocytes in S-phase (%S) , treatment of mice induced 0.46, 1.90, and 1.52 %S (males) and 2.61, 1.18, and 4.45 %S (females), which indicates that PDCB acts as an inducer of cel l. proliferation in the liver. In male rat kidney cells, the same doses pro duced 0.87, 0.67, and 1.01 %S (0.38% in controls) and in females 0.48, 0.43 , and 0.32 %S (0.52% in controls), indicating that:PDCB induces cell replic ation in the male but not the female rat kidney. Therefore, these data demo nstrate that PDCB is not genotoxic in the mouse liver or rat kidney at sing le oral doses comparable to the daily doses given in the National Toxicolog y Program (NTP) bioassay (NTP, 1987). Furthermore, the increases in RDS sup port the hypotheses that mouse liver tumor formation occurs via stimulation of hepatocyte proliferation and male rat kidney carcinogenesis via increas ed renal cell proliferation. (C) 1998 Wiley-Liss, Inc.