Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules

Namita Roy Chowdhury, Mohamed A. Saber, Pulak Lahiri, Peter I. Mackenzie, Phyllis M. Novikoff, Frederick F. Becker, Jayanta Roy-Chowdhury

Research output: Contribution to journalArticle

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Abstract

The expression of specific UDP-glucuronosyltransferase isoforms in 2-acetylaminofluorane-induced rat liver preneoplastic nodules was studied; livers from pair-fed littermates were used as controls. For comparison, liver and kidney from 3-methylcholanthrene-treated or untreated (control) rats were used. Steadystate UDP-glucuronosyltransferase mRNA levels were determined by Northern blot analysis or in situ hybridization of tissue sections using a 30-mer oligonucleotide specific for the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase (which is active toward 4-nitrophenol) or a double-stranded cDNA probe specific for androsterone-UDP-glucuronosyltransferase. For 3-methylcholanthrene-inducible UDP-glucuronosyltransferase, the mRNA level was very low in control liver; there was a 15-fold increase after 3-methylcholanthrene treatment. This mRNA was present at relatively high concentration in the kidney and there was a threefold increase after 3-methylcholanthrene administration. In livers with preneoplastic nodules 1 mo after cessation of carcinogen administration, this mRNA concentration was approximately 15 times greater than in control liver. Similar changes in the level of the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections. Immunocytochemical studies using an antiserum that recognizes the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase showed a marked increase in the concentration of this isoform in preneoplastic nodules compared with the adjacent nonnodular liver. Consistent with the changes in mRNA levels, there was a threefold increase in 4-nitrophenol-UDP-glucuronosyltransferase activity in 3-methylcholanthrene-treated rat livers and in livers with preneoplastic nodules. In contrast to the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase mRNA, the androsterone-UDP-glucuronosyltransferase mRNA was abundant in the liver and nearly absent in the kidney; its concentration was not increased after 3-methylcholanthrene administration or in preneoplastic nodules. Immunocytochemical studies using an antiserum that recognizes androsterone- testosterone- and bilirubin-UDP-glucuronosyltransferase isoforms did not show any increase of the concentration of these antigens in preneoplastic nudules. Similarly, activities for androsterone, testosterone and bilirubin also did not increase after 3-methylcholanthrene administration or in livers bearing the preneoplastic nodules.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalHepatology
Volume13
Issue number1
StatePublished - Jan 1991

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Glucuronosyltransferase
Methylcholanthrene
Carcinogens
Protein Isoforms
Liver
Messenger RNA
Androsterone
bilirubin glucuronoside glucuronosyltransferase
Kidney
In Situ Hybridization
Testosterone
Immune Sera
Bilirubin
Oligonucleotides
Northern Blotting
Complementary DNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Roy Chowdhury, N., Saber, M. A., Lahiri, P., Mackenzie, P. I., Novikoff, P. M., Becker, F. F., & Roy-Chowdhury, J. (1991). Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. Hepatology, 13(1), 38-46.

Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. / Roy Chowdhury, Namita; Saber, Mohamed A.; Lahiri, Pulak; Mackenzie, Peter I.; Novikoff, Phyllis M.; Becker, Frederick F.; Roy-Chowdhury, Jayanta.

In: Hepatology, Vol. 13, No. 1, 01.1991, p. 38-46.

Research output: Contribution to journalArticle

Roy Chowdhury, N, Saber, MA, Lahiri, P, Mackenzie, PI, Novikoff, PM, Becker, FF & Roy-Chowdhury, J 1991, 'Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules', Hepatology, vol. 13, no. 1, pp. 38-46.
Roy Chowdhury N, Saber MA, Lahiri P, Mackenzie PI, Novikoff PM, Becker FF et al. Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. Hepatology. 1991 Jan;13(1):38-46.
Roy Chowdhury, Namita ; Saber, Mohamed A. ; Lahiri, Pulak ; Mackenzie, Peter I. ; Novikoff, Phyllis M. ; Becker, Frederick F. ; Roy-Chowdhury, Jayanta. / Expression of specific UDP-glucuronosyltransferase isoforms in carcinogen-induced preneoplastic rat liver nodules. In: Hepatology. 1991 ; Vol. 13, No. 1. pp. 38-46.
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abstract = "The expression of specific UDP-glucuronosyltransferase isoforms in 2-acetylaminofluorane-induced rat liver preneoplastic nodules was studied; livers from pair-fed littermates were used as controls. For comparison, liver and kidney from 3-methylcholanthrene-treated or untreated (control) rats were used. Steadystate UDP-glucuronosyltransferase mRNA levels were determined by Northern blot analysis or in situ hybridization of tissue sections using a 30-mer oligonucleotide specific for the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase (which is active toward 4-nitrophenol) or a double-stranded cDNA probe specific for androsterone-UDP-glucuronosyltransferase. For 3-methylcholanthrene-inducible UDP-glucuronosyltransferase, the mRNA level was very low in control liver; there was a 15-fold increase after 3-methylcholanthrene treatment. This mRNA was present at relatively high concentration in the kidney and there was a threefold increase after 3-methylcholanthrene administration. In livers with preneoplastic nodules 1 mo after cessation of carcinogen administration, this mRNA concentration was approximately 15 times greater than in control liver. Similar changes in the level of the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase were also observed by in situ hybridization of tissue sections. Immunocytochemical studies using an antiserum that recognizes the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase showed a marked increase in the concentration of this isoform in preneoplastic nodules compared with the adjacent nonnodular liver. Consistent with the changes in mRNA levels, there was a threefold increase in 4-nitrophenol-UDP-glucuronosyltransferase activity in 3-methylcholanthrene-treated rat livers and in livers with preneoplastic nodules. In contrast to the 3-methylcholanthrene-inducible UDP-glucuronosyltransferase mRNA, the androsterone-UDP-glucuronosyltransferase mRNA was abundant in the liver and nearly absent in the kidney; its concentration was not increased after 3-methylcholanthrene administration or in preneoplastic nodules. Immunocytochemical studies using an antiserum that recognizes androsterone- testosterone- and bilirubin-UDP-glucuronosyltransferase isoforms did not show any increase of the concentration of these antigens in preneoplastic nudules. Similarly, activities for androsterone, testosterone and bilirubin also did not increase after 3-methylcholanthrene administration or in livers bearing the preneoplastic nodules.",
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