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EFFECTS OF SMOKING MARIJUANA, TOBACCO OR COCAINE ALONE OR IN COMBINATION ON DNA DAMAGE IN HUMAN ALVEOLAR MACROPHAGES

机译:单独或组合吸烟,大麻,烟草或可卡因对人肺泡巨噬细胞DNA损伤的影响

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This study examined the role of marijuana smoking in the pathogenesis of human lung cancer by measuring DNA damage in alveolar macrophages (AM). The alkaline unwinding method was used to determine DNA single-strand breaks in AM lavaged from non-smokers [NS] and smokers of marijuana [MS], tobacco [TS] or cocaine [CS], either alone or in combination. DNA damage was related to superoxide anion (O-2-) production by AM stimulated with phorbol myristate acetate (PMA) and to nitric oxide content of smoke using cellular nitrite (NO2-) concentrations. The percentage of double-stranded DNA present after alkaline unwinding was higher in AM of NS (41+/-5% [11]) and CS (41+/-4% [9]) versus that of MS (31+/-4% [8]), TS (35+/-3% [11]), MTS (26+/-4% [3]), and CTS (27+/-5%* [10]), mean+/-SEM [n], *=p<0.1 vs. NS). PMA stimulated O-2- production by AM from NS and CS was lower than that of other smokers, but the differences were not significant. O-2- release, however, had an inverse correlation with DNA single-strand breaks (r=-0.38,p=0.009). Nitrite content of AM from NS and CS was less than that of other smokers' cells (p<0.1 for TS & CTS vs. NS), but DNA damage had no relationship to NO2- concentration. We conclude that AM recovered from MS, either alone or in combination with tobacco smoking, show a trend towards DNA damage. Studies utilizing a larger population should verify our findings and further define its relationship to enhanced oxidant production by macrophages. [References: 21]
机译:这项研究通过测量肺泡巨噬细胞(AM)中的DNA损伤,研究了大麻在人类肺癌发病中的作用。碱性解开方法可用于测定非吸烟者[NS]和大麻[MS],烟草[TS]或可卡因[CS]的吸烟者(单独或组合使用)的AM中的DNA单链断裂。 DNA损伤与由佛波肉豆蔻酸酯乙酸酯(PMA)刺激的AM刺激产生的超氧阴离子(O-2-)和使用细胞亚硝酸盐(NO2-)浓度的烟雾中一氧化氮含量有关。 NS(41 +/- 5%[11])和CS(41 +/- 4%[9])的AM中,碱性解开后存在的双链DNA百分比高于MS(31 +/-) 4%[8]),TS(35 +/- 3%[11]),MTS(26 +/- 4%[3])和CTS(27 +/- 5%* [10]),均值+ / -SEM [n],* = p <0.1 vs. NS)。 PMA刺激的NS和CS的AM刺激O-2-生成量低于其他吸烟者,但差异不显着。然而,O-2-释放与DNA单链断裂呈负相关(r = -0.38,p = 0.009)。 NS和CS中AM的亚硝酸盐含量低于其他吸烟者细胞(TS&CTS与NS相比p <0.1),但DNA损伤与NO2浓度无关。我们得出的结论是,无论是单独使用还是与吸烟结合使用,从MS中回收的AM都显示出DNA损伤的趋势。利用大量人口的研究应证实我们的发现,并进一步定义其与巨噬细胞增强氧化剂产生的关系。 [参考:21]

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