COMPARATIVE PATTERNS OF HEPATIC DRUG-METABOLIZING-ENZYMES AND THEIR POSSIBLE CORRELATION WITH CHROMOSOMAL-ABERRATIONS IN TRANSPLANTABLE MURINE LYMPHOMA - A TIME-COURSE STUDY

The differential levels of induction of hepatic microsomal cytochrome P-450 (cyt. P-450), UDP-glucuronyl transferase (UDPGT), cytosolic glut athione-S-transferase (GSHT) activities, and major chromosomal aberrat ions were evaluated over various periods of time, following tumor tran splantation in male Swiss Albino mice. Changes in the above markers we re studied (1) to monitor the entire carcinogenic process and (2) to r est the suitability of chemopreventive exposures in terms of phase and duration of tumor growth. The microsomal cyt. P-450 content and the U DPGT activity were significantly elevated (p < 0.01-0.001) from the ea rly stages of tumor growth while the cytosolic GSHT activity reached i ts highest level (p < 0.01-0.001) only IO days after tumor transplanta tion. During the later stages of tumor growth all the biotransforming enzyme activities showed a downhill trend, which was significantly low er than that of their normal counterparts (p < 0.01-0.001). The freque ncy of different chromosomal aberrations, which were of major structur al, numerical, and physiological types, increased steadily throughout the entire length of the carcinogenic process (30 +/- 2 days).