Stimulatory effects of vitamin A analogs on induction of cell-mediated cytotoxicity in vivo
Lotan, R.; Dennert, G.
Cancer Research 39(1): 55-58
1979
ISSN/ISBN: 0008-5472 PMID: 761198 Document Number: 140319
Pretreatment of mice with small doses (25 to 300 mu g daily) of the antineoplastic agent, beta -all-trans-retinoic acid ( beta -RA), for 5 days before challenge with allogeneic tumour cells resulted in stimulated induction of cell-mediated cytotoxicity (CMC) but larger doses (500 mu g or more daily) suppressed CMC (NAR/A 48, 8267). The ability of 3 other less toxic retinoids to stimulate CMC was studied. Doses of 25, 100, 300 or 800 mu g beta -RA, trimethylmethoxyphenyl analogue of beta -RA, 13-cis-retinoic acid, or retinyl palmitate intraperitoneally daily for 5 days into C57BL/6 mice stimulated CMC 8- to 10-fold after challenge with suboptimal immunogen inoculum (106 S194 myeloma cells). When retinoid-treated mice were challenged with more tumour cells (3 X 106 or 107), CMC was also increased but to a low degree (2- to 4-fold). Stimulation of CMC by beta -RA was greatest at 100 mu g daily, while at 800 mu g daily CMC was inhibited. In contrast, the 3 other retinoids did not suppress but rather stimulated CMC even more at the largest dose tested. The trimethylmethoxyphenyl analogue had a more stimulatory effect on CMC than the other retinoids, especially in mice challenged with optimal immunogen doses.