Site-dependent modulating effects of conjugated fatty acids from saffloweroil in a rat two-stage carcinogenesis model in female Sprague-Dawley rats

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs we re examined in the post-initiation stage of a two-stage carcinogenesis mode l in female rats. Groups of 21 or 22 F344 female rats were treated sequenti ally with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7, 12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the f irst 3 weeks for initiation, and then administered diet containing 1 or 0.1 % CFA-S for 33 weeks. Further groups of animals were treated with carcinoge ns or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopatholo gically for development of preneoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In t he urinary bladder, the incidence of papillary or nodular hyperplasia but n ot tumors was significantly increased in the 1% CFA-S-treated group. The re sults indicate that low dose CFA-S may find application as a potent chemopr eventor of mammary carcinogenesis. (C) 2001 Elsevier Science Ireland Ltd. A ll rights reserved.