Differences in udp-glucuronosyltransferase activities in congenic inbred rats homozygous and heterozygous for the jaundice locus

Peter I. Mackenzie, Ida S. Owens

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The genie transfer of the jaundice locus (jj) from the Gunn rat into the inbred RHA/+ + rat produced congenic inbred homozygous RHA/jj rats which lacked detectable bilirubin UDP-glucuronosyltransferase activity. Congenic inbred RHA/j+ rats contained half the activity for bilirubin of the RHA/+ + strain. Constitutive activities for glucuronidation of sixteen substrates of twenty-one tested were inherited additively. Approximately seven groups were discernible based on the defect in activity for these substrates in the RHA/jj strain. Activity for 1-hydroxybenzo[a]pyrene was, after that for bilirubin, the most severely reduced (188-fold), while no differences in the glucuronidation of three androgens and of the 6-hydroxy-, 10-hydroxy-, and 11-hydroxybenzo[a]pyrenes were observed. The conjugation of other substrates was affected to an intermediate extent. Most of the twenty-one glucuronidating activities were induced by phenobarbital in the RHA/jj strain as well as in the RHA/ + + and RHA/j + strains. Activities for 9-hydroxybenzo[a]pyrene and for the 2-hydroxy- and 4-hydroxybiphenyls were induced such that the defect was overcome, and the RHA/jj had the same level of activity as the RHA/+ + strain. Cytochrome p-450 content and cytochrome c reductase and aminopyrine demethylase activities were unaffected in the congenic strains. Cytochrome p-450 content and cytochrome c reductase activity were induced ~2.5- and 2.0-fold, respectively, by phenobarbital while aminopyrine demethylase activity was induced about 30% in each strain. The congenic inbred rats should provide a stable and reproducible genetic model for studying defective UDP-glucuronosyltransferase specified by the jaundice (jj) locus.

Original languageEnglish
Pages (from-to)3777-3781
Number of pages5
JournalBiochemical Pharmacology
Volume32
Issue number24
DOIs
Publication statusPublished - 15 Dec 1983
Externally publishedYes

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