Citral inhibits the formation of
retinoic acid from
retinol in mouse epidermis. Since skin-
carcinogenesis is sensitive to
retinoid status, and
retinoic acid may be the active form of
vitamin A in the epidermis,
citral was tested for its ability to modulate
tumor promotion in a two-stage skin-
carcinogenesis study in hairless mice. The dorsal skins of female skh/hr1 mice were initiated with 0.1 mumol dimethylbenzanthracene, and
tumors were promoted by twice-weekly application of 10 nmol of tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Prior to each TPA application groups were dosed with 0, 1 mumol, or 10 mumol
citral.
Citral had a dose-dependent inhibitory effect on
tumor-production in the TPA promoted groups.
At 10 weeks of promotion the percentage of mice with
tumors were 88%, 72% and 60%, for the 0, 1 and 10 mumol
citral treated groups, and the numbers (mean +/- S.D.) of
tumors per affected animal were 7.3 +/- 6.6, 3.9 +/- 4.2, and 3.7 +/- 3.5, respectively. At 15 weeks of promotion the
tumor incidence was 96%, 96% and 84%, respectively, and the number of
tumors per affected animal were 9.5 +/- 6.8, 7.2 +/- 4.6 and 4.5 +/- 3.3, respectively. Again the affected mice in the high dose
citral group had significantly fewer
tumors. When the study was terminated at 20 weeks of promotion all mice had at least one
tumor, but the number of
tumors per affected mouse were lower in the
citral treated groups. These findings concur with the proposal that there is a
retinoid requirement for skin
tumor promotion, and establishes that anti-
retinoids have potential uses as modulators of
carcinogenesis.