Sex- and substrate-dependent changes in hepatic cytosolic glutathione S-transferase enzymes produced by dietary choline-deficiency.
The effect of 30 week intake of a choline-deficient (CD) diet on cytosolic glutathione S-transferase (GST) activity was investigated in rats of both sexes. GST activities in choline-supplemented (CS) control male cytosol were higher than those in CS-female cytosol for five test substrates--1-chloro-2, 4-dinitrobenzene (CDNB), 1,2-epoxy-3-(p-nitrophenoxy)-propane, trans-4-phenyl-3-buten-2-one, p-nitrobenzyl chloride (PNBC) and 1,2-dichloro-4-nitrobenzene (DCNB). The CD dietary regimen produced a relatively uniform decrease in GST activities in male liver to 37-59% of CS-control. With the exception of CDNB conjugation, GST activities in CD-male and CS-female cytosols were not significantly different. On the other hand, in female rats, the CD diet increased GST activity with PNBC and DCNB as substrates to 153 and 204% of respective CS-control female activities; other GSTs were unchanged. Hepatic cytosols from female rats were subfractionated on Whatman CM-52 and subjected to electrophoresis on polyacrylamide gels. The principal finding was that the relative concentration of GST subunit 3 (mol. wt approximately 27 kd) was apparently increased in CD-female rat cytosol; a finding that is consistent with the observed increase in DCNB- and PNBC-conjugation. Thus it is apparent that intake of the tumorigenic CD diet by male rats results in the feminization of GST activity, whereas in females GST subunit 3 is upregulated. The impaired regulation of these enzymes in CD-rats is an early event in relation to the development of hepatocellular carcinoma.
Murray
M
M
Department of Medicine, University of Sydney, NSW, Australia.
Cantrill
E
E
D000818:Animals; D002796:Choline Deficiency / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis*; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000209:etiology; D008297:Male; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013379:Substrate Specificity
D011506:Proteins; D005982:Glutathione Transferase; D005978:Glutathione