Studies on the reaction of chloromethane with preparations of liver, brain and kidney

Chloromethane reacted with rat and guinea pig brain, liver and kidney. Using 14C-CH3Cl with rat tissue homogenates, the bound radioactivity corresponded with the uptake in the liver and kidney but was lower in the brain. 14C-S-methylglutathione (GSMe) and 14C-S-methylcysteine (S-MeCys) were formed by liver, which did not hydrolyse 14C-GSMe, so that the 14C-S-MeCys must have been formed directly. Both reactions appear to be enzyme-catalysed. In the kidney and brain, 14C-S-MeCys and 14C-GSMe were formed and methylation of cysteine SH-groups in the mixed insoluble proteins was demonstrated. Traces of radioactivity were found in methionine in the kidney proteins. The kidney and brain homogenates hydrolysed 14C-GSMe. Rapid losses of radioactivity during processing in some kidney experiments suggest that volatile products are formed, but this is not due to fission of S-methyl groups of S-MeCys or GSMe. The level of binding was lower in heated tissues, especially in the water-soluble fraction. Inhibition of respiration of rat brain and inhibition of two thiol-dependent enzymes could not be demonstrated. It is suggested that loss of GSH and intracellular accumulation of GSMe may account for some of the clinical features of intoxication.