The group I aziridinylquinone anti-cancer agents mitomycin C, diaziquo
ne or trenimon were much more cytotoxic to DT-diaphorase-enriched L517
8Y/HBM10 lymphoblasts than parental L5178Y cells and caused little oxy
gen activation. Furthermore, inactivation of cellular DT-diaphorase pr
evented cytotoxicity whereas catalase did not affect cytotoxicity. Thi
s suggests that DT-diaphorase activated these agents and the hydroquin
one formed mediated DNA alkylation, crosslinking and cytotoxicity. The
group LI quinone agents phenanthrenequinone, 2-amino-1,4-naphthoquino
neimine or naphthazarin were also more cytotoxic to L5178Y/HBM10 cells
than parental cells and caused considerable oxygen activation. Inacti
vation of DT-diaphorase, however, prevented both oxygen activation and
cytotoxicity. Furthermore added catalase decreased cytotoxicity, wher
eas catalase inactivation enhanced cytotoxicity. This suggests that DT
-diaphorase activated these agents and the hydroquinone formed caused
extensive oxygen activation sufficient to cause DNA oxidative damage a
nd cytotoxicity. The group III quinone agents menadione, 2,3-dimethoxy
-1,4-naphthoquinone and 2,6-dimethoxy-benzoquinone, on the other hand,
were more cytotoxic to the parental cells than L5178Y/HBM10 cells and
caused less oxygen activation than group II agents. Furthermore, inac
tivation of DT-diaphorase enhanced cytotoxicity and prevented oxygen a
ctivation than group II agents. Oxygen activation was therefore also a
ttributed to hydroquinone autoxidation. However catalase did not affec
t cytotoxicity towards parental cells. This suggests that DT-diaphoras
e detoxified group III quinones and that cytotoxicity may involve DNA
oxidative damage by the semiquinone radicals.