Benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene differentially affect bone marrow cells of the lymphoid and myeloid lineages.
Polycyclic aromatic hydrocarbons (PAHs) are common environmental contaminants that are carcinogenic and immunosuppressive. Benzo(a)pyrene (BP) and 7,12-dimethylbenz(a)anthracene (DMBA) are two prototypic PAHs known to impair the cell-mediated and humoral immune responses. We have previously shown that, in C57BL/6J mice, total bone marrow (BM) cellularity decreased two-fold following intraperitoneal DMBA treatment but not BP treatment. Here, we have used flow cytometry to demonstrate that BP and DMBA differentially alter the lymphoid and myeloid lineages. Following DMBA treatment, the pro/pre B-lymphocytes (B220(lo)/IgM(-)) and the immature B-lymphocytes (B220(lo)/IgM(+)) significantly decreased, while the mature B-lymphocytes (B220(hi)/IgM(+)) remained unaffected. In contrast, BP treatment decreased the pro/pre B-lymphocytes, and did not affect the immature B-lymphocytes or mature B-lymphocytes. The Gr-1(+) cells of the myeloid lineage were depleted 50% following DMBA treatment and only minimally depleted following BP treatment. Interestingly, the monocytes (7/4(+)1A8(lo)) and neutrophils (7/4(+)1A8(hi)) within this Gr-1(+) population were differentially affected by these PAHs. Monocytes and neutrophils were depleted following DMBA treatment whereas neutrophils decreased and monocytes increased following BP treatment. Although TNFalpha and CYP1B1 are implicated as essential mediators of hypocellularity, the similar induction of TNFalpha mRNA and CYP1B1 mRNA in the BM by BP and DMBA suggests that they are not limiting factors in mediating the different effects of these PAHs. Given that similar amounts of BP and DMBA reach the BM when administered intraperitoneally, their differential effects on the lymphoid and myeloid lineages probably stem from differences in reactive metabolites such as PAH quinones and PAH-dihydrodiol-epoxides.
Galván
Noé
N
Molecular and Environmental Toxicology, University of Wisconsin, 1300 University Avenue, Madison, 53706, USA.
Page
Todd J
TJ
Czuprynski
Charles J
CJ
Jefcoate
Colin R
CR
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000235:genetics; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002452:Cell Count; D019070:Cell Lineage; D065633:Cytochrome P-450 CYP1B1; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D007165:Immunosuppression Therapy; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects*; D023461:Myeloid Progenitor Cells / Q000187:drug effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics
D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1