A survey of the response of different strains of mice to substances metabolised by microsomal oxidation; hexobarbitone, zoxazolamine and warfarin

Abstract

Sixteen strains of mice were compared with respect to their hexobarbitone sleeping time and their zoxazolamine paralysis time. The strains were A2G, CBA, CE, C3H, C57BL, C57L. DBA, F/st, ICFW, NNRI, NZB, Schneider Simpson, SM, TO and 129/Rr. All the strains except 129/Rr were also for survival on a diet containing 0.05% racemic Warfarin.There was highly significant interstrain correlation between hexobarbitone sleeping time and zoxazolamine paralysis time (r = 0.72) and between hexo barbitone sleeping time and Warfarin survival (r = 0.68). There was a significant correlation between zoxazolamine paralysis time and Warfarin survival (r = 0.56).The correlations can be explained if: (1) there is a genetically determind interstrain variable which is some common component of the microsomal mixed-function oxidase systems involved in the hydroxylation of the three substances; (2) the anticoagulant action of Warfarin is caused more by a hydroxylated melabolite of Warfarin than by Warfarin itself.Phenobarbitone pretreatment shortened hexobarbitone sleeping times and zoxazolamine paralysis times, but its effect was geater in those strains with longer initial hexobarbitone sleeping times and zoxazolamine paralysis time. Piperonyl butoxide pretreatment lengthened hexobarbitone sleeping times, but had no effect on zoxazolamine paralysis times. Warfarin survival was unaltered by pretreatment with either phenobarbital or piperonyl butoxide.