Influence of strain differences in mice on the metabolism and toxicity of benzene

Chronic benzene exposure results in a progressive depression of bone marrow function and is thought to be caused by a metabolite of benzene (Snyder and Kocsis, 1975; Goldstein and Laskin, 1977). Several reports concerning differences in xenobiotic metabolism and toxicity among inbred strains of mice prompted us to study benzene metabolism and toxicity in C57BL/6 and DBA/2 mice. DBA/2 mice were more susceptible to benzene than C57BL/6 mice. No differences in the total amount of urinary benzene metabolites produced were found between the strains; however, differences in the relative amounts of specific metabolites were noted. DBA/2 mice produced more phenylglucuronide but less ethereal sulfate conjugates than C57BL/6 mice. Hydrolysis of the urinary conjugates revealed that DBA/2 mice excreted more phenol, but less hydroquinone than C57BL/6 mice. Multiple dose studies revealed that the more resistant C57BL/6 mice contained less water soluble benzene metabolites in bone marrow, liver, kidney, blood, spleen, and lung than DBA/2 mice. C57BL/6 mice also contained less covalently bound metabolites in bone marrow, blood, spleen, and muscle than DBA/2 mice following multiple doses of benzene. V_max values for UDPGA utilization in C57BL/6 mice were almost six times the V_max values observed for DBA/2 mice. Furthermore, V_max values for phenylsulfate formation in C57BL/6 mice were three times the V_max values for DBA/2 mice. It was concluded that the difference in susceptibility to benzene between C57BL/6 and DBA/2 mice was not the result of a single factor, buth rather, the sum total of a number of metabolic events.