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McArdle Laboratory for Cancer Research, Medical Center, University of Wisconsin, Madison, Wisconsin 53706
Benzpyrene hydroxylase activity and its induction by a single injection of methylcholanthrene (2 mg/100 g body weight) were studied in liver from rats during developmental stages and in Morris Hepatomas 9618A, 9633, 7800, 7794A, and 8999 under controlled feeding conditions. The purpose of the experiment was to see whether naturally occurring levels of benzpyrene hydroxylase are lower in activity among the different hepatoma lines than in adult liver or newborn liver and whether induced levels of the activity in hepatoma by methylcholanthrene treatment could be referred to those induced in liver from rats of normal developmental stages.
Benzpyrene hydroxylase activity in Hepatoma 9633 is very low, but after administration of methylcholanthrene the activity was markedly increased, with some modification by variations in the time of injection. The benzpyrene hydroxylase activities in the host livers were strongly influenced by the size of the pooled hepatoma in rats bearing Hepatoma 8999 but not in rats bearing Hepatoma 9618A, while in the latter an influence of feeding regimen was shown.
Methylcholanthrene was able to induce benzpyrene hydroxylase activity in Morris hepatomas as well as in the corresponding host liver, although the induced levels in hepatomas were always lower than those in the host liver. There was no consistency of the induced levels among hepatoma lines, although all the rats were sacrificed exactly 6 hr after onset of feeding under controlled dietary regimens and 24 hr after a single intraperitoneal treatment with methylcholanthrene.
Benzpyrene hydroxylase in fetal rat liver was very low in activity, and after birth a marked increase was observed. After administration of methycholanthrene the fetal liver showed some increase in benzpyrene hydroxylase activities and in neonatal stages more profound responses were detected. The activity of benzpyrene hydroxylase and the magnitude of the induced levels in normal rat liver were completely dependent upon the age of the rat, and there were no differences in activity between male and female rats until after 21 days of age. The similarity of hepatoma lines to normal rat liver during developmental stages with respect to the activity of benzpyrene hydroxylase and its response to methylcholanthrene induction were discussed.
1 This study was supported in part by Departmental Grant CA-07175 and Training Grant T01-CA-5002 from the National Cancer Institute, USPHS. This paper is the sixth in the series entitled, "The Comparative Enzymology and Cell Origin of Rat Hepatomas."
2 Postdoctoral fellow, Damon Runyon Memorial Fund for Cancer Research, 1966 to 1968. Present address: The Research Institute for Tuberculosis, Leprosy and Cancer, Tohoku University, Sendai, Japan.
3 Present address: Department of Biochemistry, College of Medicine, Howard University, Washington, D. C. 20001. Supported in part by USPHS Grant No. CA-10729.
Received 1/10/69. Accepted 5/26/69.
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