Diethylnitrosamine-induced increase in gamma-glutamyltranspeptidase in rat liver: its association with thyroid hormone deficiency and its reversal by tri-iodothyronine.
1. The nodular phase of hepatic premalignancy was induced in male Fischer 344 rats by the administration of diethylnitrosamine, 200 mg/kg i.p., followed by promotion utilizing the Solt-Farber promoting regime. 2. Relative to the situation in normal non-treated control rats: the activity of gamma-glutamyltranspeptidase was found to be increased 9.42-fold in homogenate and 7.33-fold in plasma membrane fractions prepared from the livers of saline-injected control rats; and 81.37-fold in homogenates and 91.92-fold in plasma membranes prepared from the livers of diethylnitrosamine-injected rats; plasma levels of total T3 and total T4 were found to be decreased 42.06 and 47.45% in saline-injected control rats and 88.7 and 83.2% in diethylnitrosamine-injected rats, respectively. 3. An early pre-nodular phase of hepatic premalignancy was produced in young immature and mature adult male Fischer 344 rats by the administration of diethylnitrosamine, 75 mg/kg, without subsequent application of the promotion regime. 4. Relative to the situation in control rats: the activity of gamma-glutamyltranspeptidase was found to be increased in liver homogenates prepared from diethylnitrosamine-treated rats, 1.62-fold in young immature rats 1.20-fold in mature adult rats; plasma levels of total T3 were found to be reduced in diethylnitrosamine-treated rats, 28% in young immature rats 9% in mature adult rats. 5. Treatment of diethylnitrosamine-injected young immature male Fischer 344 rats at the prenodular phase of hepatic premalignancy with tri-iodothyronine at 0.005 micrograms/kg s.c. daily for 7 days reversed the diethylnitrosamine-induced increase in liver homogenate gamma-glutamyltranspeptidase activity and the decrease in plasma total T3, restoring these parameters to normal levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
S J
SJ
Sulakhe
V B
VB
Pulga
S T
ST
Tran
D000375:Aging / Q000378:metabolism; D000818:Animals; D004052:Diethylnitrosamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D013963:Thyroid Hormones / Q000172:deficiency / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D013963:Thyroid Hormones; D014284:Triiodothyronine; D004052:Diethylnitrosamine; D005723:gamma-Glutamyltransferase