Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars:: Implications for risk assessment
Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars:: Implications for risk assessment
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DOI：
10.1289/ehp.98106s61325
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发表时间：
1998-12-01
影响因子：
10.4
通讯作者：
Rodriguez, LV
中科院分区：
文献类型：
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作者：
Goldstein, LS;Weyand, EH;Rodriguez, LV
目前估计煤焦油等多环芳烃（PAH）复杂混合物的定量癌症风险的方法假定，总体效力可以从苯并[a]芘（B[a]P）等几种致癌成分的浓度中获得。遗传毒性损伤，如DNA加合物，被认为是PAH诱导的肿瘤发生的一个重要方面，并可能是一个生物标志物，用于估计风险的暴露。然而，B[a]P在肿瘤发生中的作用和加合物形成的关系尚未在适用于人类健康风险评估的模型中进行严格测试。因此，我们直接比较了B[a]P和煤焦油在几个实验方案中的肿瘤诱导和加合物形成，包括被监管机构广泛接受和使用的方案。我们发现，B[a]P含量并不占暴露于煤焦油后的肿瘤发病率。DNA加合物中发现的谣言和无肿瘤组织和肿瘤的结果是不能预测的总DNA加合物或由B[a] P形成的DNA加合物的定量。这些数据表明，基于B[a]P含量的风险评估可能无法准确预测环境多环芳烃对人类健康造成的风险。
Current methods to estimate the quantitative cancer risk of complex mixtures of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that overall potency can be derived from knowledge of the concentration of a few carcinogenic components such as benzo[a]pyrene (B[a]P). Genotoxic damage, such as DNA adducts, is thought to be an essential aspect of PAH-induced tumorigenesis and could be a biomarker for exposure useful for estimating risk. However, the role of B[a]P and the relationship of adduct formation in tumorigenesis have not been tested rigorously in models appropriate for human health risk assessment. Therefore, we directly compared tumor induction and adduct formation by B[a]P and coal tars in several experimental protocols, including one broadly accepted and used by regulators. We found that B[a]P content did not account for tumor incidences after exposure to coal tars. DNA adducts were found in both rumors and tumor-free tissue and tumor outcomes were not predicted by either quantitation of total DNA adducts or by the DNA adduct formed by B[a]P. These data suggest that risk assessments based on B[a]P content may not predict accurately risk to human health posed by environmental PAH.