Increase of UDP-glucuronosyltransferase activities toward xenobiotics during the development of hereditary hepatitis in LEC rats.

UDP-glucuronosyltransferase activities were induced spontaneously during the development of hepatitis in LEC (Long Evans Cinnamon-like coat color) rats. Transition of hepatic microsomal UDP-glucuronosyltransferase activities was observed during the development of the LEC rat, which displayed spontaneous fulminant hepatitis with severe jaundice at about 12-16 weeks after birth. UDP-glucuronosyltransferase activities toward various substrates in 8-week-old LEC and LEA (Long Evans Agouti coat color; control) rats were similar. After 8 weeks of age, the transferase activities of LEA rats towards all substrates tested, except for bilirubin, decreased slightly during the next 24 weeks. In LEC rats, the transferase activities towards serotonin and several phenolic xenobiotics, such as 4-nitrophenol, 1-naphthol and 4-methylumbelliferone, but not 4-hydroxybiphenyl, increased about 2-fold at 16 weeks of age. During the 24 weeks following the first 8 weeks of age, the high level activities towards the xenobiotics continued, with the exception of bilirubin transferase activity which decreased gradually. These results suggest that a form of UDP-glucuronosyltransferase, which catalyzes the glucuronidations of serotonin and these xenobiotics except for 4-hydroxybiphenyl, is induced during the development of hepatitis in the LEC rat.