Site-dependent modulating effects of conjugated fatty acids from safflower oil 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 were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially 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 first 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 carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic 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 the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.
Kimoto
N
N
First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan.
Hirose
M
M
Futakuchi
M
M
Iwata
T
T
Kasai
M
M
Shirai
T
T
D019813:1,2-Dimethylhydrazine; D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced; D019787:Linoleic Acid / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D009369:Neoplasms / Q000473:pathology*; D009602:Nitrosamines; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012450:Safflower Oil / Q000494:pharmacology*; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002273:Carcinogens; D005227:Fatty Acids; D009602:Nitrosamines; D002085:Butylhydroxybutylnitrosamine; C012457:diisopropanolnitrosamine; D015127:9,10-Dimethyl-1,2-benzanthracene; D012450:Safflower Oil; D019787:Linoleic Acid; D005982:Glutathione Transferase; D019813:1,2-Dimethylhydrazine