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5332001 
Technical Report 
Biodegradation Of Alpha-hexachlorocyclohexane. I. Glutathione-Dependent Conversion To A Hydrophilic Metabolite By Rat Liver Cytosol 
Portig, J; Kraus, P; Sodomann, S; Noack, G 
1973 
1 
Naunyn-Schmiedeberg's Archives of Pharmacology
ISSN: 0028-1298
EISSN: 1432-1912 
279 
2 
185-198 
English 
4129542 
The biodegradation of alpha-hexachlorocyclohexane (319846) (HCH) by liver cytosol was studied in Wistar-rats. Liver homogenates were prepared from animals treated orally with 10 milliliters (ml) per kilogram body weight of a 2 percent HCH solution. Cytosol was prepared from the homogenates; some portions were dialyzed or gel filtered. To assess HCH degradation, assays were conducted with varying amounts of protein and substrate. Labeled HCH was used, and the amount of radioactivity in the aqueous layer after centrifugation was taken as the measure of HCH degradation. When cytosol preparations containing 10 to 15 milligrams/ml of protein were incubated with 10 micrograms (microg)/ml of labeled HCH for 2 hours at 37 degrees-C and in the presence of air, between 5 and 10 percent of the added radioactivity, regardless of label, was consistently rendered water soluble, or was no longer extracted from the incubation mixture with a nonpolar solvent that took up all unchanged HCH. The percentage of conversion could be increased by extending the time of incubation, by using a more alkaline pH, and by using cytosol prepared from rat livers pretreated with HCH. However, since the physical properties of HCH did not permit the use of initial concentrations much higher than 10microg/ml, the absolute amounts of product formed even under optimum conditions were only in the range of a few microg/ml of cytosol. The authors conclude that rat liver cytosol converts HCH to a hydrophilic metabolite by a process that apparently is enzymic, has a specific requirement for glutathione, and involves dechlorination. This process is also susceptible to stimulation by pretreatment with the drug itself.