Glutathione transferases in rat lung: the presence of transferase 7-7, highly efficient in the conjugation of glutathione with the carcinogenic (+)-7?,8?-dihydroxy-9?,10?-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene
The enzyme-catalysed conjugation of (±)-7β,8α-dihydroxy-9α,10α-oxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [(±)- anti -BPDE] with glutathione (GSH) by cytosolic GSH transferases isolated primarily from rat lung has been studied. GSH transferase 4-4 was active in the GSH conjugation of anti -BPDE, whereas transferases 2-2 and 3-3 showed little activity. GSH transferase 1-1 did not contribute to the activity since significant amounts were not detected in the rat lung. Activity was also obtained with several acidic pulmonary GSH transferases and with a newly described form, transferase 7-7, also isolated from rat kidney and from hyperplastic liver nodules. The catalytic efficiency ( kcat / Km ) of transferase 7-7 was seven times that of transferase 4-4, the most active rat transferase previously identified. When the GSH concentration was varied at constant (±)- anti -BPDE concentration in the presence of transferases 4-4, 7-7 or the major acidic transferase, non-linear Lineweaver-Burk plots were obtained. Resolution of the GSH conjugates of the two enantiomers of (±)- anti -BPDE by h.p.l.c. showed that all isoenzymes with notable activity were selective (≧97%) for the (+)-enantiomer of anti -BPDE, which is generally considered to be the most carcinogenic form of BPDE. The possibility that one enan-tiomer inhibits the conjugation of the other enantiomer with GSH cannot be excluded and may quantitatively affect the results obtained.