ENZYMATIC PATTERN OF PRENEOPLASTIC AND NEOPLASTIC LESIONS INDUCED IN THE KIDNEY OF CBA MICE BY 1,2-DIMETHYLHYDRAZINE

Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subc utaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and ser ial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen content, basophilia, and the activ ities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucos e-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (GBPDH), h exokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), mal ic enzyme (ME), succinate dehydrogenase (SDH), alkaline phosphatase (A LPase) and gamma-glutamyltranspeptidase (GGT). RCTs displayed the same histochemical profile irrespective of their size and growth pattern. In comparison with the normal kidney epithelium, the neoplastic cells exhibited elevated activities of enzymes for glycolysis (HK, PK, LDH) and the pentose phosphate pathway (G6PDH), while negative G6Pase and l ow SDH activity were observed in these cells. The majority of RCTs sho wed high PHO activity and weak staining for SYN. Activities of ALPase and GGT were negative in most of the RCTs. Markedly enlarged eels with atypical nuclei were detected in some advanced RCTs. Higher activitie s of glycolytic and mitochondrial enzymes and G6PDH were found in thes e enlarged cells than in other tumor cells. Tubular preneoplastic lesi ons were similar to neoplastic lesions in morphological and histochemi cal characteristics. The present study revealed that a markedly elevat ed capacity for glycolysis and the pentose phosphate pathway occurred in RCTs in mice. A similar histochemical pattern in the few preneoplas tic tubular lesions observed suggests that these metabolic aberrations emerge early during carcinogenesis, but additional studies on early s tages of renal carcinogenesis are needed to substantiate this assumpti on.