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Modifying effects of docosahexaenoic acid (DHA) were examined using a medium-term multi-organ carcinogenesis model (DMBDD model). Groups of twenty F344 male rats were treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), 1,2-dimethylhydrazine (DMH, s.c.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) and dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) during the first 4 weeks (DMBDD treatment), and then DHA-ethyl ester (DHA-E), DHA-triglyceride (DHA-TG) and/or tocopherol were administered intragastrically 3 times a week for 31 weeks. Significant inhibition of the development of glutathione S-transferase placental form (GST-P) positive foci was observed in DMBDD treated 30% DHA-TG 404 mg and 128 mg + tocopherols groups and with tocopherol alone; however, this appeared to be due to the tocopherol. DHA treatment did not influence the development of aberrant crypt foci in the large intestine. Histopathologically, the incidences of preneoplastic and neoplastic lesions in other organs were also not increased or decreased by DHA treatment. Thus, the results indicate a lack of chemopreventive and tumor promotion effects of any type of DHA in male rats under the present experimental conditions.

journal of toxicologic pathology

Lack of Chemoprevention or Promotion Effects of Docosahexaenoic Acid on Small Intestine, Colon, Liver, Lung, Thyroid, Esophagus, Kidney, and Forestomach Carcinogenesis in a Rat Medium-Term Multi-Organ Carcinogenesis Model