Comparison of early injury to liver endoplasmic reticulum by halomethanes, hexachloroethane, benzene, toluene, bromobenzene, ethionine, thioacetamide and dimethylnitrosamine

This study compares the effects in vivo of CH2Cl2, CH2Br2, CHCl3, CH2I2, CHBr3, CCl4, CHI3, CBr4, CI4, C2Cl6, C2HCl5, C6H6, C7H8, C6H5Br, ethionine, thioaeetamide and dimethylnitrosamine on the functions and composition of liver endoplasmic reticulum 2 hr after poisoning. Within the halomethane series, the effects on lipid diene conjugate content, oxidative demethylase, 14C-glycine incorporation into protein and glucose 6-phosphatase of liver microsomes and cell sap RNA content, increase with decreasing effective negative charge on the halogen atoms (ϵ), an indicator of increasing halomethane free radical reactivity (cf.B. P. Dailey, J. chem. Phys.33, 1641,1960). Peak toxic effect is reached following CCl4 and CHI3. Glycine incorporation into protein is also decreased 2 hr after thioacetamide and dimethylnitrosamine. After dimethylnitrosamine, suppression of protein synthesis is concomitant with increases in lipid diene conjugate content and cell sap RNA. C6H5Br and ethionine, both known hepatotoxins, do not effect microsomal composition and function at this time, nor do C6H6 or C7H8 both organic solvents with solubility properties similar to CCl4. The findings support the hypothesis that free radical halomethane metabolites injure the endoplasmic reticulum by reacting with and chemically altering its constituents. While dimethylnitrosamine may act similarly, thioaeetamide, bromobenzene and ethionine apparently do not.