Fluoranthene induces programmed cell death and alters growth of immature B cell populations in bone marrow cultures.
Many studies have demonstrated that polycyclic aromatic hydrocarbons adversely affect mature mammalian immune systems. However, little is known about the cellular mechanism(s) mediating this immunosuppression or the potential for these ubiquitous environmental chemicals to similarly compromise lymphocyte development (lymphopoiesis). Murine bone marrow cultures were exploited in the present studies to evaluate the potential for fluoranthene, a mutagenic, cocarcinogenic, polycyclic aromatic hydrocarbon, to modulate B cell lymphopoiesis. In this well characterized system, interactions between immature bone marrow-derived precursor B (preB) cells and bone marrow-derived stromal cells closely mimic preB-stromal cell interactions in vivo and resemble interactions between other bone marrow-derived hematopoietic cells and their supporting stroma. Data presented herein indicate that: (i) fluoranthene suppresses B lymphopoiesis within 2 days in bone marrow cultures; (ii) fluoranthene suppresses lymphopoiesis at least in part by direct interactions with preB cells; (iii) fluoranthene lymphotoxicity is mediated by rapid induction of DNA fragmentation characteristic of programmed cell death (apoptosis) and (iv) preB cell populations surviving the initial death signal or preB cell populations exposed to lower doses of fluoranthene (0.5-5 micrograms/ml) exhibit altered growth and survival characteristics. The data suggest several levels at which fluoranthene could compromise B lymphopoiesis.
Hinoshita
F
F
Department of Pathology, Harvard Medical School, Boston, MA.
Hardin
J A
JA
Sherr
D H
DH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000633:toxicity*; D006410:Hematopoiesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D005449:Fluorenes; C007738:fluoranthene; D004247:DNA