INHIBITORS OF EICOSANOID BIOSYNTHESIS AND THEIR EFFECT UPON BACILLUS-THURINGIENSIS DELTA-ENDOTOXIN RESPONSE IN CULTURED INSECT CELLS AND DEVELOPING LARVAE

Twelve inhibitors of eicosanoid biosynthesis were examined for their a bility to affect the response of insect cells in vitro and developing larvae to delta-endotoxin from Bacillus thuringiensis. The response of cultured insect cells from Manduca sexta, Choristoneura fumiferana, a nd Plodia interpunctella to CryIA(c) and CryIC protein from Bacillus t huringiensis was measured while exposed to various concentrations of s pecific cyclooxygenase and/or lipoxygenase inhibitors. Five of the inh ibitors (curcumin, baicalein, nordihydroguaiaretic acid, indomethacin, and eicosatetraynoic acid) were toxic to the cells at high concentrat ions (> 20 mu M). Surprisingly, the same inhibitors had no significant effect upon normal larval development, except for nordihydroguaiareti c acid. No true, consistent difference was detected with either lipoxy genase or cyclooxygenase inhibitors for cells or larvae treated with d elta-endotoxin. However, the delta-endotoxin response of insect cells in vitro and developing larvae in the presence of nordihydroguaiaretic acid was strong evidence of an involvement with P-450 cytochromes in the B. thuringiensis toxic response.