The detection of in vivo hematotoxicity of benzene by in vitro liquid bone marrow cultures

Abstract

Bone marrow toxicity induced by benzene inhalation was investigated in mice using an in vitro bone marrow culture system and a bioassay for leukemia. Donor animals (6-week-old female C56B1/6J) were exposed to 400 ppm benzene 6 hr/day for either 9 days (5 days/week) or for 11 consecutive days. Cell suspensions from long-term bone marrow cultures established from benzene-exposed mice showed a progressive reduction in the number of spleen colony-forming cells (the hematopoietic stem cell) compared to control. Different combinations of adherent cell layers and reinoculated cells showed that cultures containing bone marrow cells from benzene-exposed mice had a lower capacity to maintain stem cell proliferation than normal combinations irrespective of whether benzene-exposed marrow was in the adherent cell layers or reinoculated cells. These results indicate that benzene inhalation produces stem cell injury leading to diminished self-replication and derangement of the adherent marrow population. Bone marrow cultures from benzene-treated mice did not develop detectable transformation in vitro throughout the culture period. Neonatal mice inoculated with cultured cells from benzene-exposed mice have not developed leukemia during an 8-month period after inoculation.