Use of in vitro assays to assess hematotoxic effects of environmental compounds.
The number of chemicals being introduced into the environment increases and many of these substances may pose a health risk to exposed individuals. Many environmental toxicants with a potential toxicity to the hematopoietic system have been identified by animal experiments. Owing to the risks of severe chronic hematopoietic disorders, it is important to screen chemicals for their hematotoxicity. The aim of this work was to identify, through the use of in vitro techniques, targets for hematotoxic effects. Our study focused on myeloid and erythroid hematopoietic progenitors and stromal stem cells as possible targets. The in vitro assays showed that various hematotoxic compounds exert different effects on these cell populations. In vitro exposure of murine bone marrow cells to various inorganic (cadmium, lead) and organic (benzene metabolites, lindane. benzo-[a]-pyrene (BaP), PCB (polychlorinated biphenyl) congeners) environmental chemicals indicated that hematopoietic or stromal bone marrow cells were targets for most of the chemicals. Stromal cells were more affected by lead, cadmium, and BaP compared to myeloid cells. Benzene and phenol gave no response, but the metabolites catechol and hydroquinone were equally toxic to the stromal and the myeloid progenitor cells. Among the PCBs tested, PCB126 was most toxic. Human progenitor cells derived from cord blood were exposed in vitro to catechol, hydroquinone, lead nitrate, and PCBs. Human hematopoietic cells were sensitive to the tested compounds. Human erythroid progenitors are more susceptible to lead exposure than are myeloid progenitors. Based on the in vitro tests, humans are more sensitive to lead, catechol, and PCB126 than are mice. In contrast to the murine data, humans responded with individual differences to lead and PCB126.
Van Den Heuvel
R L
RL
VITO, Flemish Institute for Technological Research, Department of Environmental Toxicology, Mol, Belgium. rosette.vandenheuvel@vito.be
Leppens
H
H
Schoeters
G E
GE
D016475:3T3 Cells; D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity; D001580:Benzopyrenes / Q000737:chemistry / Q000633:toxicity; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D019187:Cadmium Compounds / Q000633:toxicity; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D015386:Hazardous Substances / Q000633:toxicity*; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000633:toxicity; D006801:Humans; D007854:Lead / Q000633:toxicity; D051379:Mice; D009566:Nitrates / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D018675:Toxicity Tests
D001580:Benzopyrenes; D019187:Cadmium Compounds; D015386:Hazardous Substances; D009566:Nitrates; D007854:Lead; D001556:Hexachlorocyclohexane; C017461:lead nitrate; D011078:Polychlorinated Biphenyls; D001554:Benzene; C035196:cadmium nitrate