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Laboratory of Pathophysiology, Life Sciences Division, IIT Research Institute, Chicago, Illinois 60616
Administration of a dietary retinoid supplement beginning 1 week after carcinogen administration is highly effective in the inhibition of rat mammary carcinogenesis. A study was designed at two carcinogen dose levels to determine to what extent retinoid feeding can be delayed and retain its chemoprotective effect. In the high-dose experiment, groups of 30 virgin female Sprague-Dawley rats received a single i.v. dose of 50 mg N-methyl-N-nitrosourea (MNU) per kg body weight and were fed a dietary supplement of 328 mg retinyl acetate per kg diet beginning at 1, 4, or 8 weeks after MNU administration. In the low-dose experiment, groups of 50 rats received 25 mg MNU per kg, and the retinoid was begun at 1, 4, 8, 12, 16, or 20 weeks post-MNU. Controls at both dose levels received a placebo diet beginning 1 week after carcinogen treatment. At the high MNU dose, retinyl acetate was most effective in inhibition of carcinogenesis when treatment was begun 1 week after MNU administration. Delaying retinyl acetate feeding until 4 weeks post-MNU resulted in slightly reduced chemoprotective efficacy, while an 8-week delay caused a complete loss of anticancer activity. At the low MNU dose, delaying retinyl acetate administration for up to 12 weeks after MNU administration caused no loss of chemopreventive efficacy. A 16-week delay resulted in decreased anticancer activity, while retinoid treatment begun 20 weeks post-MNU had no effect on cancer induction. Retinoid administration can be delayed beyond 1 week and retain its activity against rat mammary carcinogenesis; the length of delay allowable without loss of activity is a function of tumor latency.
1 Supported in part by National Cancer Institute Contracts N01-CB-74207, N01-CP-23292, and N01-CP-15742.
2 To whom requests for reprints should be addressed.
Received 1/15/82. Accepted 4/13/82.
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