ENZYME DEVIATION PATTERNS IN PRIMARY RAT HEPATOMAS INDUCED BY SEQUENTIAL ADMINISTRATION OF 2 CHEMICALLY DIFFERENT CARCINOGENS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (10) , 4147-4153
Abstract
Enzyme deviation patterns were examined in primary rat hepatomas induced by short-term sequential administration of 2 chemical carcinogens from among 2-fluorenylacetamide (FAA), diethylnitrosamine (DENA) and 3''-methyl-4-dimethylaminoazobenzene (3''-Me-DAB) or by FAA or 3''-Me-DAB followed by phenobarbital as a promoter. The purpose was to discern how the patterns are influenced by different administration schedules of carcinogens and which of the 2 carcinogens in the sequence affects the patterns more. Biochemical differentiation of hyperplastic hepatic nodules and hepatomas was determined by simultaneous assays of activities and isozyme composition of glucose-adenosine triphosphate phosphotransferase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and .gamma.-glutamyltransferase with consideration of histological classification of nodules and tumors. Poorly differentiated hepatomas were predominantly induced by 3''-Me-DAB followed by FAA or DENA except for hepatomas induced by 3''-Me-DAB followed by phenobarbital, which were mainly well and moderately differentiated; well and moderately differentiated hepatomas were predominantly induced by FAA followed by 3''-Me-DAB or phenobarbital. The degree of enzyme deviation of the hepatomas induced by DENA as the 1st carcinogen was intermediate between those of hepatomas induced by FAA or 3''-Me-DAB although the degree tended to increase with increased dose or term of DENA. Deviations of some enzymes (pyruvate kinase and fructose-1,6-bisphosphatase) and histological differentiation of the primary hepatomas are apparently more strongly influenced by the 1st carcinogen than by the 2nd under these administration schedules. The degree of enzyme deviation shown by hepatomas produced by a particular carcinogen treatment regimen probably relates principally to the potential of that regimen to induce the more anaplastic tumors.