Glutathione S-
transferases (
GSTs) of female A/J mouse lung have been purified and characterized for their (a) structural interrelationships, (b) substrate specificities toward the ultimate carcinogenic metabolite of
benzo(a)pyrene (BP), (+)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-anti-
BPDE], and (c) induction by three naturally occurring organosulfides (OSCs)-from garlic [
diallyl sulfide (
DAS),
diallyl trisulfide (DATS) and
dipropyl sulfide (DPS)], which significantly differ in their efficacy against BP-induced
lung cancer in mice. The GST activity in the lung was due to two alpha class (pI 9.4 and 6.0), two mu class (pI 8.7 and 8.6), and one pi class (pI 8.9)
isoenzyme. The GST
isoenzyme profile of the lung was different from that of the A/J mouse forestomach, which also is a target organ for BP-induced
cancer in mice. Noticeably, an alpha class heterodimeric
isoenzyme (pI 9.5) present in the forestomach of A/J mouse, which is exceptionally efficient in the
glutathione (GSH) conjugation of (+)-anti-
BPDE [X. Hu, S.K. Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271, 32684-32688], could not be detected in the lung. The specific activities of the lung
GSTs in the GSH conjugation of (+)-anti-
BPDE were in the order of GST 8.9 > GST 8.7 > GST 9.4 > GST 6.0. While DPS treatment did not increase the levels of any pulmonary GST
isoenzyme, the expression of pi class GST 8.9 was significantly increased in response to both
DAS and DATS administrations. Interestingly, DATS, an OSC which lacks activity against BP-induced
lung cancer in mice, was a relatively more potent inducer of pi class GST
isoenzyme than
DAS, which is a potent inhibitor of BP-induced lung
tumorigenesis. The results of the present study suggest that a mechanism(s) other than GST induction is likely to be responsible for the differential effects of
DAS and DATS on BP-induced
lung cancer in mice. Our results also suggest that relatively lower efficacies of the OSCs against BP-induced
lung cancer than against forestomach
neoplasia may be attributed to (a) a lack of expression in the lung of an
isoenzyme corresponding to forestomach GST 9.5 and (b) a comparatively lower level of induction of pi type GST in the lung than in the forestomach by these OSCs.