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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1980 Apr;77(4):2251–2254. doi: 10.1073/pnas.77.4.2251

Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

T J Slaga, A J Klein-Szanto, S M Fischer, C E Weeks, K Nelson, S Major
PMCID: PMC348691  PMID: 6769125

Abstract

The effects of fluocinolone acetonide (FA), retinoic acid (RA), and tosylphenylalanine chloromethyl ketone (TPCK) on two-stage promotion after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female Sencar mice were investigated. The two-stage promotion protocol was achieved by twice weekly applications of 2 microgram of 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2 weeks (stage I) followed by twice weekly applications of mezerein for 18 weeks (stage II). Separately stage I and II do not cause any tumors to develop after DMBA initiation. FA was found to be a potent inhibitor of stages I and II but to a greater degree for stage I than for stage II. RA was ineffective in stage I but was a potent inhibitor of stage II; TPCK specifically inhibited stage I but not stage II. FA and TPCK effectively counteract the appearance of the dark basal keratinocytes, whereas RA has no effect. These results provide additional evidence for the importance of dark basal keratinocytes in stage I of promotion and indicate that most of the other biochemical and morphological responses normally associated with promotion (such as polyamines) are actually associated with stage II of promotion.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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