INCREASE OF UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES TOWARD XENOBIOTICSDURING THE DEVELOPMENT OF HEREDITARY HEPATITIS IN LEC RATS

UDP-glucuronosyltransferase activities were induced spontaneously duri ng the development of hepatitis in LEC (Long Evans Cinnamon-like coat color) rats. Transition of hepatic microsomal UDP-glucuronosyltransfer ase activities was observed during the development of the LEC rat, whi ch displayed spontaneous fulminant hepatitis with severe jaundice at a bout 12-16 weeks after birth. UDP-glucuronosyltransferase activities t oward various substrates in 8-week-old LEC and LEA (Long Evans Agouti coat color; control) rats were similar. After 8 weeks of age, the tran sferase activities of LEA rats towards all substrates tested, except f or bilirubin, decreased slightly during the next 24 weeks. In LEC rats , the transferase activities towards serotonin and several phenolic xe nobiotics, 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 lev el activities towards the xenobiotics continued, with the exception of bilirubin transferase activity which decreased gradually. These resul ts 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.