Differences in quinone reductase activity in primary bone marrow stromal cells derived from C57BL/6 and DBA/2 mice.
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.
Twerdok
L E
LE
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Trush
M A
MA
D000818:Animals; D016227:Benzoquinones; D001853:Bone Marrow / Q000201:enzymology*; D001854:Bone Marrow Cells; D006873:Hydroquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019800:Phenol; D010636:Phenols / Q000633:toxicity; D011808:Quinone Reductases / Q000096:biosynthesis / Q000378:metabolism*; D011809:Quinones / Q000633:toxicity; D013045:Species Specificity
D016227:Benzoquinones; D006873:Hydroquinones; D010636:Phenols; D011809:Quinones; D019800:Phenol; C004532:quinone; C018855:2-tert-butylhydroquinone; D011808:Quinone Reductases; C031927:hydroquinone