Induction of peroxisome proliferation in the liver of biphenyl-fed female mice.

Biphenyl has been widely used as a heat-transfer agent, a dye mordant, a synthetic resin, a constituent of agricultural chemicals and a post-harvest fungicide to preserve citrus fruits. Occupational biphenyl poisoning has been characterized by disorders of the liver, kidney, central and peripheral nervous systems and motor and muscle functions. The carcinogenic potential of biphenyl was not evaluated or classified by the Japan Society of Occupational Health (JSOH) or the International Agency for Research on Cancer (IARC). In the previous paper, however, we reported that the feeding of rats with a biphenyl-containing diet for 2 yr induced bladder tumors in close association with formation of bladder calculi. It was demonstrated in the submitted companion paper (unpublished data) that hepatocellular carcinomas (control: 1/50, 667 ppm: 5/50, 2,000 ppm: 7/50, 6,000 ppm: 5/49) and adenomas (control: 2/50, 667 ppm: 3/50, 2,000 ppm: 12/50, 6,000 ppm: 10/49) were induced in the female mice fed biphenyl-containing diets for 2 yr, but not in male mice. It is well known that many peroxisome proliferators induce hepatocellular tumors in rodents. In an attempt to explore any causative factor for biphenyl-induced hepatocellular tumors in female mice, this electron microscopic study was designed to determine if feeding female mice a biphenyl-containing diet for 13 wk induces peroxisome proliferation in the liver. We report here on the occurrence of peroxisome proliferation in the hepatocytes of female mice fed a biphenyl-containing diet for 13 wk.