The effect of the time and duration of retinoid treatment on the inhibition of Stage II tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was studied in CD-1 mice. All mice were initiated with 400 nmol of benzo(a)pyrene and received Stage I tumor promotion (3.2 nmol of TPA twice weekly for 2 wk). Animals were then randomized into groups which received 13-cis-retinoic acid during early, middle, or late Stage II promotion. 13-cis-Retinoic acid pretreatments starting on Day 1, Wk 8, or Wk 23 of Stage II promotion resulted in 47, 28, or 19% inhibition, respectively, of TPA-induced tumor formation. One-half of the mice receiving 13-cis-retinoic acid at Day 1 or Wk 8 were removed from the retinoid treatments at Wk 23, the time of cessation of TPA promotion. The inhibition of tumor formation remained constant during the 15-wk observation period after cessation of retinoid treatment, suggesting that retinoid inhibition of mouse skin tumor promotion is stable in the absence of further promotion and preceded the step of irreversible conversion of promoter dependence to promoter independence.


This investigation was supported by NIH Grant CA-27502.

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