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氧化多核芳香烃菲烯酮的细菌和人类细胞致突变性以及小鼠肺肿瘤发生性

Bacterial and human cell mutagenicity and mouse lung tumorigenicity of the oxygenated polynuclear aromatic hydrocarbon phenalenone.

作者信息

Wang J S, Busby W F

机构信息

Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139, USA.

出版信息

Fundam Appl Toxicol. 1996 Oct;33(2):212-9. doi: 10.1006/faat.1996.0158.

DOI:10.1006/faat.1996.0158
PMID:8921339
Abstract

Phenalenone (perinaphthenone) is a major oxygenated polynuclear aromatic hydrocarbon (oxy-PAH) atmospheric pollutant formed from the combustion of fossil fuels. Mutagenicity of phenalenone was measured in quantitative forward mutation assays with Salmonella typhimurium TM677 and metabolically competent human B-lymphoblastoid cell lines (MCL-5 and h1A1v2 cells), and its tumorigenicity was also assessed in a newborn mouse assay. Phenalenone was mutagenic in Salmonella in the presence of rat liver postmitochondrial supernatant (PMS) at a minimum detectable mutagen concentration (MDMC) of 12 micrograms/ml, but was not mutagenic in the absence of PMS at concentrations up to 100 micrograms/ ml. Phenalenone was not significantly mutagenic in either human cell line after 28 hr treatment, although mutant fractions were increased by nearly fivefold in h1A1v2 cells (at the tk locus) exposed at 30 micrograms/ml. However, after 72 hr treatment, phenalenone was mutagenic at the hprt locus in h1A1v2 cells with an MDMC of 3 micrograms/ml. Phenalenone was also tumorigenic in male BLU:Ha mice with a lung tumor incidence of 33% 6 months after injection with 4.2 mg phenalenone, the highest dose tested. Lung tumor multiplicity in this treatment group was 0.5 tumor/mouse. No increase in lung tumors in female mice was observed. Indices of lung tumor incidence (ED50) and multiplicity (TM1.0) for male mice were 29.3 and 34.9 mumol, respectively. These data suggest that phenalenone does not contribute significantly to the mutagenicity or carcinogenicity of combustion emission extracts.

摘要

菲萘酮(苊烯酮)是一种主要的含氧多环芳烃(oxy-PAH)大气污染物,由化石燃料燃烧形成。采用鼠伤寒沙门氏菌TM677和具有代谢活性的人B淋巴母细胞系(MCL-5和h1A1v2细胞)进行定量正向突变试验,测定了菲萘酮的致突变性,并在新生小鼠试验中评估了其致癌性。在存在大鼠肝脏线粒体后上清液(PMS)的情况下,菲萘酮在沙门氏菌中具有致突变性,最低可检测致突变浓度(MDMC)为12微克/毫升,但在不存在PMS的情况下,浓度高达100微克/毫升时无致突变性。经过28小时处理后,菲萘酮在两种人类细胞系中均无显著致突变性,尽管在暴露于30微克/毫升的h1A1v2细胞(在tk基因座处)中,突变分数增加了近五倍。然而,经过72小时处理后,菲萘酮在h1A1v2细胞的hprt基因座处具有致突变性,MDMC为3微克/毫升。菲萘酮对雄性BLU:Ha小鼠也具有致癌性,注射4.2毫克菲萘酮(测试的最高剂量)6个月后,肺肿瘤发生率为33%。该治疗组的肺肿瘤多发性为0.5个肿瘤/小鼠。未观察到雌性小鼠肺肿瘤增加。雄性小鼠的肺肿瘤发生率(ED50)和多发性(TM1.0)指数分别为29.3和34.9微摩尔。这些数据表明,菲萘酮对燃烧排放提取物的致突变性或致癌性贡献不大。

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