The effect of omega-6 and omega-3 fatty acids on 3H-thymidine incorporation in hepatoma 7288CTC perfused in situ.
Ingestion of diets containing corn oil or marine fish oils is known to increase or decrease, respectively, the growth of transplantable rodent tumours. The active agents in these oils have been identified as linoleic acid (in corn oil) and omega-3 fatty acids (in marine oils), but it is still not known how they influence the tumour growth processes. In these experiments we examined the effects of plasma free omega-6 and omega-3 fatty acids on the rate of 3H-thymidine incorporation in tissue-isolated hepatoma 7288CTC perfused in situ. Host Buffalo rats were fed an essential fatty acid-deficient diet. Plasma and tumours in these animals contained low endogenous levels of both omega-6 and omega-3 fatty acids. Perfusion of these tumours for 2 h with donor whole blood containing added omega-6 free fatty acids, including 0.5 mM linoleic (C18:2,N-6), gamma-linolenic (C18:3,N-6), dihomo-gamma-linolenic (C20:3,N-6) or arachidonic acids (C20:4,N-6), increased the rate of 3H-thymidine incorporation. Linoleic acid was about three times more effective than the other omega-6 fatty acids. Typical hyperbolic substrate-saturation curves were observed as the plasma free linoleate or arachidonate concentration was increased. When perfused alone plasma free omega-3 fatty acids had no effect on tumour 3H-thymidine incorporation, but in the presence of linoleic acid the omega-3 fatty acids, alpha-linolenic (C18:3,N-3) and eicosapentaenoic (C20:5,N-3), competitively inhibited both tumour linoleate uptake and the stimulative effect on 3H-thymidine incorporation. The results suggest that the ambient plasma free linoleic and arachidonic acid concentrations in host arterial blood directly influence the rate of tumour DNA synthesis. Plasma free omega-3 fatty acids appear to modulate the effect of linoleic acid by competitively inhibiting its uptake. These relationships could explain the actions of dietary linoleic and omega-3 fatty acids on tumour growth in vivo.
Sauer
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Cancer Research Laboratory, Mary Imogene Bassett Hospital, Cooperstown, New York 13326.
Dauchy
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D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects*; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011915:Rats, Inbred BUF; D013936:Thymidine / Q000378:metabolism*
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D013936:Thymidine