Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on lipid peroxidation in microsomal systems in vitro.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) when added to suspensions of rat hepatic microsomes in the presence of NADPH has little influence on the peroxidation of microsomal lipids unless the system also contains complexed ferric ion, in which case TCDD stimulates. This stimulation does not appear to require metabolism of the TCDD. Peroxidation was monitored by production of thiobarbiturate-reactive substances (malondialdehyde and dienals), production of conjugated dienes, and disappearance of polyunsaturated fatty acids. Stimulation of lipid peroxidation by TCDD in a mixed lysosome-microsome preparation resulted in significantly decreased 'leakage' of acid phosphatase into the medium, implying an effect on lysosomal membranes. Consideration both of the present results and data in the literature leads to the conclusion that it is premature to attempt to define the relationship between enzyme induction, lipid peroxidation and TCDD lethality.