Granville Courtney A, Hanley Nancy M, Mumford Judy L, DeMarini David M
Department of Environmental Science and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA.
Mutat Res. 2003 Apr 9;525(1-2):77-83. doi: 10.1016/s0027-5107(02)00314-7.
Nonsmoking women in Xuan Wei County, Yunnan Province, China who use smoky coal for cooking and heating in poorly ventilated homes have the highest lung cancer mortality rate in China, and their lung cancer is linked epidemiologically to their use of smoky coal. The emissions contain 81% organic matter, of which 43% is polycyclic aromatic hydrocarbons (PAHs). Exposure assessment and molecular analysis of the lung tumors from nonsmoking women who use smoky coal strongly indicate that PAHs in the emissions are a primary cause of the elevated lung cancer in this population. Here we have determined the mutation spectra of an extract of smoky coal emissions in Salmonella TA98 and TA100; the extract was not mutagenic in TA104. The extract was 8.7 x more mutagenic in TA100 with S9 than without (8.7 rev/microg versus 1.0 rev/microg) and was >3 x more mutagenic in TA100 than in TA98--consistent with a prominent role for PAHs in the mutagenicity of the extract because PAHs are generally more mutagenic in the base-substitution strain TA100 than in the frameshift strain TA98. The extract induced only a hotspot mutation in TA98; another combustion emission, cigarette smoke condensate (CSC), also induces this single class of mutation. In TA100, the mutation spectra of the extract were not significantly different in the presence or absence of S9 and were primarily (78-86%) GC --> TA transversions. This mutation is induced to a similar extent by CSC (78%) and the PAH benzo[a]pyrene (B[a]P) (77%). The frequency of GC --> TA transversions induced in Salmonella by the extract (78-86%) is similar to the frequency of this mutation in the TP53 (76%) and KRAS (86%) genes of lung tumors from nonsmoking women exposed to smoky coal emissions. The mutation spectra of the extract reflect the presence of PAHs in the mixture and support a role for PAHs in the induction of the mutations and tumors due to exposure to smoky coal emissions.
在中国云南省宣威县，不吸烟的女性在通风不良的家中使用烟煤做饭和取暖，她们的肺癌死亡率是中国最高的，并且从流行病学角度来看，她们的肺癌与使用烟煤有关。这些排放物含有81%的有机物，其中43%是多环芳烃（PAHs）。对使用烟煤的不吸烟女性的肺部肿瘤进行暴露评估和分子分析，有力地表明排放物中的PAHs是该人群肺癌发病率升高的主要原因。在此，我们测定了烟煤排放物提取物在沙门氏菌TA98和TA100中的突变谱；该提取物在TA104中无致突变性。该提取物在有S9时在TA100中的致突变性比无S9时高8.7倍（8.7回复突变/微克对1.0回复突变/微克），并且在TA100中的致突变性比在TA98中高3倍以上——这与PAHs在提取物致突变性中起主要作用一致，因为PAHs通常在碱基置换菌株TA100中比在移码菌株TA98中更具致突变性。该提取物在TA98中仅诱导出一个热点突变；另一种燃烧排放物，香烟烟雾冷凝物（CSC），也诱导这类单一突变。在TA100中，无论有无S9，提取物的突变谱均无显著差异，且主要是（78 - 86%）GC→TA颠换。CSC（78%）和多环芳烃苯并[a]芘（B[a]P）（77%）在相似程度上诱导这种突变。提取物在沙门氏菌中诱导的GC→TA颠换频率（78 - 86%）与接触烟煤排放物的不吸烟女性肺部肿瘤中TP53（76%）和KRAS（86%）基因的这种突变频率相似。提取物的突变谱反映了混合物中PAHs的存在，并支持PAHs在因接触烟煤排放物而诱导突变和肿瘤方面所起的作用。
