This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lotan, R. Articles by Dennert, G. Search for Related Content PubMed PubMed Citation Articles by Lotan, R. Articles by Dennert, G.

Stimulatory Effects of Vitamin A Analogs on Induction of Cell-mediated Cytotoxicity in Vivo¹

Department of Developmental and Cell Biology, University of California, Irvine, California 92717 [R. L.], and The Salk Institute for Biological Studies, San Diego, California 92112 [G. D.]

Previously, we observed that pretreatment of mice with low doses (25 to 300 µg/mouse/day) of the antineoplastic agent, ß-all-trans-retinoic acid (ß-RA), for 5 days before challenge with allogeneic tumor cells resulted in stimulated induction of cell-mediated cytotoxicity (CMC) but that higher doses (500 µg/mouse/day) suppressed CMC. The present study examined the ability of three other less toxic retinoids to stimulate CMC. Administration of 25-, 100-, 300-, or 800-µg/mouse/day i.p. doses of ß-RA, trimethylmethoxyphenyl analog of ß-RA, 13-cis-retinoic acid, or retinyl palmitate daily for 5 days into C57BL/6 mice stimulated CMC to 8- to 10-fold after challenge with suboptimal immunogen inoculum (10⁶ S194 myeloma cells/mouse). When retinoid-treated mice were challenged with a higher number of tumor cells (3 x 10⁶ or 10⁷/mouse), CMC was also enhanced; however, it was to a low degree (2- to 4-fold). Optimal stimulation of CMC by ß-RA occurred at 100 µg/mouse/day, while at 800 µg/mouse/day CMC was somewhat inhibited. In contrast, the three other retinoids did not suppress but rather stimulated CMC even better at the highest dose tested. The trimethylmethoxyphenyl analog exhibited a higher stimulatory effect on CMC than did the other retinoids, especially in mice challenged with optimal immunogen doses. These results demonstrate that, in addition to ß-RA, other retinoids are capable of enhancing CMC. This property may in part mediate their reported antineoplastic activity.

¹ This investigation was supported by Grants CA-15581, CA-19334 (to G. Dennert), and CA-22823 (to G. L. Nicolson and R. Lotan) awarded by the National Cancer Institute and Department of Health, Education & Welfare.

² Recipient of Lievre Senior Fellowship D-295 from the California Division, Inc., American Cancer Society. To whom requests for reprints should be addressed.

Received 12/19/77. Accepted 10/11/78.