Inhibition of both stage I and stage II mouse skin tumour promotion by retinoic acid and the dependence of inhibition of tumor promotion on the duration of retinoic acid treatment.

Retinoic acid is a potent inhibitor of mouse skin tumor promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). We have further evaluated the effect of retinoic acid on the stages of tumor promotion and also analyzed the effect of duration of retinoic acid treatment on mouse skin tumor promotion by TPA. In a number of independent experiments, either with female CD-1 or SENCAR mice, we failed to observe a specificity of inhibition by retinoic acid of either Stage I or Stage II tumor promotion. In a typical experiment with SENCAR mice, application of 34 nmol of retinoic acid concurrently with each application of either TPA (3.2 nmol) or mezerein (3.2 nmol) to initiated (with 10 nmol 7,12-dimethylbenz(a)anthracene) skin equally inhibited promotion of skin papilloma formation. Furthermore, sustained inhibition of tumor promotion by retinoic acid required a continuous application of retinoic acid in conjunction with each promotional treatment with TPA; if retinoic acid treatment was discontinued, TPA treatment elicited tumor formation. These results indicate: (a) retinoic acid inhibits both Stage I and Stage II of tumor promotion; and (b) inhibition of tumor promotion exhibits retinoic acid dependency.