Benzene myeloclastogenicity: a function of its metabolism.
Using the micronucleus test we have found no significant difference between germ-free and conventional (non-germ-free) male CD-1 mice gavaged twice with 440 or 880 mg benzene/kg. Hence, the higher myeloclastogenicity observed previously with the p.o. (4-6 times) than with the i.p. route of benzene administration was ruled out as being due to the involvement of gut flora in benzene biotransformation. Pretreatment of males with 3-methylcholanthrene or beta-naphthoflavone, inducers of P-448 monooxygenase, but not phenobarbital, an inducer of P-450, significantly enhanced the myeloclastogenic effect of a single oral dose of benzene (440 mg/kg). Single oral doses of phenol, catechol, or hydroquinone (250, 150, and 200 mg/kg, respectively) failed to reproduce the potent myeloclastogenic effect of benzene. In fact, only hydroquinone was mildly clastogenic. The relation between benzene's myeloclastogenicity and metabolism is discussed.
D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D001571:Benzoflavones / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects* / Q000648:ultrastructure; D002396:Catechols / Q000494:pharmacology; D002869:Chromosome Aberrations / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005856:Germ-Free Life; D006873:Hydroquinones / Q000494:pharmacology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D019800:Phenol; D010636:Phenols / Q000494:pharmacology; D012737:Sex Factors; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D002396:Catechols; D006873:Hydroquinones; D010636:Phenols; D019800:Phenol; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D006899:Mixed Function Oxygenases; D001554:Benzene; C034221:catechol; C031927:hydroquinone; D010634:Phenobarbital