The level of
quinone oxidoreductases (microsomal and cytosolic
DT-diaphorase,
NADPH-cytochrome P450 reductase and
NADH-cytochrome b5 reductase),
superoxide dismutase and
glutathione-related enzymatic activities in
diethylstilbestrol (DES)-induced
carcinogenesis in kidney from Syrian golden hamsters are presented. Animals that exhibited two different stages of DES-induced
carcinogenesis in kidney--pre- and neoplastic lesions and tumorous lesions (after 6 and 8 months of continuous exposure to DES respectively)--were studied in comparison to kidneys from control animals. A dramatic decrease in microsomal and cytosolic
DT-diaphorase activities (13.6 and 37.8% of controls), as well as in
glutathione disulphide
reductase (39.5%), and less marked in
superoxide dismutase (45.6%),
NADH cytochrome b5 reductase (61.9%)
glutathione transferase (GST) towards
1-chloro-2,4-dinitrobenzene (CDNB) (66.2%) and
glutathione peroxidase (GSH-Px) (80%) activities, were observed in kidneys with pre- and neoplastic lesions.
NADPH-cytochrome P450 reductase and GST activity towards 4-hydroxy-2,3-trans-nonenal (4-HNE) showed no statistically significant variation at this stage of
carcinogenesis. In kidney from animals with tumorous lesions, all the enzymatic activities mentioned above decreased, except for
superoxide dismutase, which was increased to 186% of the control activity. GST activity towards 4-HNE again showed no statistically significant variation. These results suggest that if one-electron reduction of diethylstilbestrol-4',4''-quinone (DESQ) occurs, it may play a very important role in the development of DES
carcinogenesis (pre- and neoplastic lesions), since at this stage of
carcinogenesis the primary defense mechanisms against the
oxygen free radicals generated in this way, i.e. SOD activity, is reduced to less than a half of control values. Both cytosolic and microsomal
DT-diaphorase activities are unable at this stage of
carcinogenesis to promote effectively the two-electron reduction of DESQ, which would avoid the initial formation of
superoxide anion. The consequences of these decreases may be an increased steady-state concentration of
superoxide anion and
hydrogen peroxide, which in the presence of
iron might lead to lipid peroxidation. GST activity towards 4-HNE could be responsible for the possible higher steady-state concentration of this lipid peroxidation product during DES treatment. The induction of
DT-diaphorase and its protective role in the prevention of the development of pre- and neoplastic lesions in kidney from Syrian golden hamster during DES treatment is also discussed.