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 β‐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.