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The effects of n-3 α-linolenic acid-rich perilla oil (P-oil) or n-6 linoleic acid-rich corn oil (C-oil) and indomethacin (IM), either alone or in combination, were examined in a rat medium-term multiorgan carcinogenesis model. Male F344 rats were given N-diethylnitrosamine (DEN), N-methyl-nitrosourea (MNU), N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN), N-nitrosobis (2-hydroxypropyl) amine (DHPN) and 1,2- dimethylhydrazine (DMH) during the initial 4 weeks as initiators. This was followed by additional of 10% each of P-oil or C-oil to each their diet, alone or with IM 40 ppm in their drinking water for, 32 weeks. The animals were sacrificed at week 36, and proliferative lesions in major organs, such as the liver, kidney, lung and colon, were examined histopathologically. IM significantly lowered the multiplicity of colon tumors. P-oil tended to lower the incidences and multiplicities of colon tumors while C-oil tended to increase them. Additional treatment with IM caused further decreases in animals receiving P-oil, but the effect was less than additive. In the C-oil group, additional treatment with IM nullified its enhancing effect. In the lung, C-oil weakly increased the incidence and multiplicity of lung tumors. However, this was again suppressed by additional treatment with IM. While perilla oil and IM alone did not influence lung and renal carcinogenesis, their combination again enhanced carcinogenesis in the lung and kidney. In the liver, P-oil or C-oil alone significantly decreased the number and/or area of GST-P positive foci, while additional treatment with IM tended to nullify the decrease. These results suggest that IM exerts different modifying effects in the presence of different fats in the diet.

Combined Chemopreventive Effects of Perilla or Corn Oil and Indomethacin in a Rat Medium-Term Multiorgan Carcinogenesis Model