Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment
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- 作者：Ian W.H. Jarvis ; ian.jarvis@ki.se" class="auth_mail ; Kristian Dreij ; Å ; se Mattsson ; Bengt Jernströ ; m ; Ulla Stenius
- 关键词：AhR ; aryl hydrocarbon receptor ; ATM ; ataxia telangiectasia mutated ; ATR ; ataxia telangiectasia and Rad3-related protein ; B[a]P ; benzo[a]pyrene ; B[a]Peq ; B[a]P-equivalent ; Chk1 ; checkpoint kinase 1 ; CT ; coal tar ; CYP ; cytochrome P450 ; DE ; diol epoxide ; DNA-PK ; DNA-dependent protein kinase ; DPE ; diesel particulate extract ; DPM ; diesel particulate matter ; EFSA ; European Food Safety Agency ; H2AX ; H2A histone family member X ; HEL ; human embryonic lung ; IARC ; International Agency for Research on Cance
- 刊名：Toxicology
- 出版年：3 July 2014
- 年：2014
- 卷：321
- 期：Complete
- 页码：27-39
- 全文大小：1643 K
文摘
In this review we discuss the effects of exposure to complex PAH mixtures in vitro and in vivo on mechanisms related to carcinogenesis. Of particular concern regarding exposure to complex PAH mixtures is how interactions between different constituents can affect the carcinogenic response and how these might be included in risk assessment. Overall the findings suggest that the responses resulting from exposure to complex PAH mixtures is varied and complicated. More- and less-than additive effects on bioactivation and DNA damage formation have been observed depending on the various mixtures studied, and equally dependent on the different test systems that are used. Furthermore, the findings show that the commonly used biological end-point of DNA damage formation is insufficient for studying mixture effects. At present the assessment of the risk of exposure to complex PAH mixtures involves comparison to individual compounds using either a surrogate or a component-based potency approach. We discuss how future risk assessment strategies for complex PAH mixtures should be based around whole mixture assessment in order to account for interaction effects. Inherent to this is the need to incorporate different experimental approaches using robust and sensitive biological endpoints. Furthermore, the emphasis on future research should be placed on studying real life mixtures that better represent the complex PAH mixtures that humans are exposed to.