Summary
Six diploid and three other Morris hepatomas, and the corresponding host livers, were assayed under controlled dietary and feeding regimens for certain enzymes known to show marked variations in activity in normal liver under the specified conditions. The purpose of the experiment was to determine whether the hepatomas that were minimally deviated with respect to karyotype would respond to environmental variations in a manner similar to normal liver and, incidentally, to determine whether there was evidence of tumor-host interaction as reflected in the enzyme patterns of the host livers.
Tyrosine transaminase activity in normal rat liver showed wide variation depending on the protein content of the diet and the feeding pattern, with a sharp maximum about 6 hours after the beginning of the feeding period. The activities in the various hepatomas ranged from almost zero in 9618A to values greatly exceeding that of normal liver in hepatoma 5123C; in most cases the activities were quite unresponsive to dietary protein, and the amplitude of daily variation was in general less than in normal liver. The activities of this enzyme in host livers were not greatly different from those in normal liver.
Serine dehydratase activity in normal rat liver showed wide variation depending on the protein content of the diet but was not greatly affected by the time of day in the case of rats fed for 8 hours out of each 24. The activities in the hepatomas varied widely from almost zero in the six diploid hepatomas to higher than normal levels in 5123C and to intermediate levels in 9108 and 7794B, with the latter three hepatoma lines insensitive to variations in the protein contents of the diet, as was the case with tyrosine transaminase. There was a significant decrease in serine dehydratase activity in the host livers of several of the hepatoma lines, including those with high activities.
In general, glucose-6-phosphate dehydrogenase showed increased activity in all hepatoma lines, citrate cleavage enzyme showed very low activity, and glycogen was present in extremely low amounts. Morris hepatoma 9618A was exceptional in having near normal levels of citrate cleavage enzyme and glycogen in the middle range for normal liver.
In both liver and hepatomas there appeared to be a reciprocal relationship between glucose-6-phosphate dehydrogenase and serine dehydratase, with each enzyme tending to be low in activity when the activity of the other enzyme was high. However, the activities of the enzymes in liver could vary over a remarkably wide range, depending on circumstances, whereas the activities of the two enzymes in each hepatoma appeared to be restricted to a very narrow range characteristic of that hepatoma line.
The aggregate impression of great variation in enzyme pattern in the hepatomas must be moderated by the realization that the activities fall within ranges covered by normal fetal, neonatal, or adult liver, and, in fact, the hepatomas are not nearly so responsive to environmental factors as is adult liver. Several of the enzymes appear to be noninduced in some hepatoma lines, derepressed in other lines, and in all cases studied, one or more of the enzymes resist alteration in activity in response to environmental change.
This study was supported in part by Departmental Grant CA-07125 and Training Grant T01-CA-5002 from the National Cancer Institute, USPHS. We cannot undertake to supply reprints of this report.
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