Toxicity of autoxidized squalene and linoleic acid, and of simpler peroxides, in relation to toxicity of radiation

Abstract

An anaerobic reagent is described, consisting of leuco brilliant cresyl blue in butanol buffered with lutidine and lutidine acetate, with and without lithium cuprobromide. This shows 2 types of reaction with various organic peroxides, according to the effect of the cuprobromide, with further differentiation according to kinetics. Both types of reaction were obtained equally, with the products of uncatalyzed autoxidation of squalene and linoleic acid at room temperature, at all stages observed, but the autoxidation of linoleic acid was highly erratic. The previous finding of 2 types of peroxide in extracts of X-irradiated mice can now be explained in terms of linoleic acid as well as of squalene. On a basis of total peroxide content, autoxidized linoleic acid, unlike autoxidized squalene, was more toxic by intraperitoneal injection than any of the simple peroxides with which it was compared. Autoxidized methyl linileate was less toxic than most of the simple peroxides. The LD50 of autoxidized linoleic acid (0.26 [mu]mole of peroxide/g) was only slightly higher than the mean increase of peroxide previously found in mice after 950 r of X-rays (0.22 [mu]mole/g). Injected peroxides kill more quickly than radiation, but this may be a question of distribution. The evidence is consistent with the view that radiation toxicity is due to initiation of chain autoxidation of essential fatty acids producing lethal doses of peroxides in sites not reached by vitamin E.