Twerdok L E, Trush M A
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Res Commun Chem Pathol Pharmacol. 1990 Mar;67(3):375-86.
DBA/2 mice have been reported to be more susceptible than C57BL/6 mice to the bone marrow toxic effects of two quinone-generating chemicals, benzo[a]pyrene and benzene. In this study we have investigated the activity of quinone reductase (QR) (NADPH:DT diaphorase), a quinone detoxifying enzyme, in whole bone marrow and bone marrow-derived stromal cells from these two strains of mice. The sensitivity of bone marrow-derived stromal cells to toxicity induced by several metabolites of benzene was also investigated. Whole bone marrow and primary cultures of stromal cells cultured from DBA/2 mice had a lower basal level of QR activity compared to those of C57Bl/6 mice and as such exhibited a greater sensitivity to the toxic effects of hydroquinone (HQ), a metabolite of benzene. However, there was no difference between the two strains of mice to benzoquinone- or phenol-induced toxicity. Increased QR activity in DBA/2 and C57Bl/6 stromal cells could be induced by prior stromal cell treatment with tert-butylhydroquinone which resulted in protection against subsequent hydroquinone treatment. Thus, differences in target organ QR activity may contribute to differential susceptibility to quinone-generating bone marrow toxins.
