Benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene differentially affect bone marrow cells of the lymphoid and myeloid lineages
Benzo(a)pyrene and 7,12-dimethylbenz(a)anthrecene differentially affect bone marrow cells of the lymphoid and myeloid lineages
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DOI：
10.1016/j.taap.2005.09.018
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发表时间：
2006-06-01
影响因子：
3.8
通讯作者：
Jefcoate, Colin R.
中科院分区：
文献类型：
--
作者：
Galvan, Noe;Page, Todd J.;Jefcoate, Colin R.
多环芳烃（PAHs）是常见的环境污染物，具有致癌性和免疫抑制性。苯并（a）芘（BP）和7，12-二甲基苯并（a）蒽（DMBA）是两种典型的多环芳烃，已知会损害细胞介导和体液免疫反应。我们以前已经表明，在C57 BL/6 J小鼠中，总骨髓（BM）细胞减少了2倍后，腹腔内DMBA治疗，但BP治疗。在这里，我们使用流式细胞术来证明BP和DMBA差异改变淋巴和骨髓谱系。DMBA处理后，前/前B淋巴细胞（B220（lo）/IgM（-））和未成熟B淋巴细胞（B220（lo）/IgM（+））显著减少，而成熟B淋巴细胞（B220（hi）/IgM（+））未受影响。与此相反，BP处理减少前/前B淋巴细胞，不影响未成熟B淋巴细胞或成熟B淋巴细胞。骨髓谱系的Gr-1（+）细胞在DMBA处理后被耗尽50%，并且在BP处理后仅被最低限度地耗尽。有趣的是，单核细胞（7/4（+）1A 8（lo））和嗜中性粒细胞（7/4（+）1A 8（hi））在这个Gr-1（+）人口的不同影响，这些多环芳烃。DMBA处理后单核细胞和中性粒细胞减少，而BP处理后中性粒细胞减少，单核细胞增加。虽然TNF α和CYP 1B 1被认为是细胞减少的重要介质，但BP和DMBA对BM中TNF α mRNA和CYP 1B 1 mRNA的类似诱导表明它们不是介导这些PAH不同作用的限制因素。考虑到当腹膜内给药时BP和DMBA达到BM的量相似，它们对淋巴和骨髓谱系的不同作用可能源于反应性代谢物如PAH醌和PAH-二氢二醇-环氧化物的差异。
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 TNF alpha and CYP1B1 are implicated as essential mediators of hypocellularity, the similar induction of TNF alpha 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.