The present study was designed to further investigate the role of
reactive oxygen species in the mechanism of action of
anthrone tumor promoters. To accomplish this, the effects of several
antioxidants on the induction of epidermal
ornithine decarboxylase (ODC) activity, epidermal
hyperplasia, skin
edema, and skin
tumor promotion by
chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) were tested.
Ascorbyl palmitate (AP), given 5 min prior to the promoter at 1 and 4 mumol doses, effectively inhibited the induction of ODC activity (28% and 59%, respectively) by 220 nmol of
chrysarobin. Using a similar protocol,
alpha-tocopherol acetate (alpha-TA)
at 10 and 40 mumol doses also effectively inhibited the induction of ODC activity (36% and 70%, respectively) by 220 nmol of
chrysarobin. In contrast,
butylated hydroxyanisole (
BHA) at doses up to 56 mumol per mouse was ineffective at inhibiting the induction of ODC by
chrysarobin. AP at the 4 mumol dose significantly inhibited the induction of
edema by
chrysarobin by 24% and the induction of epidermal
hyperplasia by 23%. alpha-TA at the 40 mumol dose also significantly inhibited
chrysarobin-induced
edema by 22% and epidermal
hyperplasia by 17%. Skin
tumor promotion in mice initiated with 25 nmol of 7,12-dimethylbenz[a]
anthracene and promoted with once-weekly treatments of 220 nmol
chrysarobin was markedly inhibited by treating mice with either AP or alpha-TA 5 min prior to promoter treatment. AP at 1 and 4 mumol doses significantly reduced the number of
papillomas per mouse, by 48% and 44%, respectively. alpha-TA
at 10 and 40 mumol doses also significantly reduced the number of
papillomas per mouse, by 33% and 59%, respectively. In two separate
tumor experiments,
BHA at 2.8 and 5.6 mumol failed to inhibit
chrysarobin tumor promotion. The current results provide further support for a role of
reactive oxygen species in the
tumor promoting activity of
anthrones. In addition, the data indicate that the phenolic
antioxidant BHA is an ineffective inhibitor of
anthrone tumor promotion.