Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment.
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.
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. Electronic address: ian.jarvis@ki.se.
Ian W H
IW
Jarvis
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Kristian
K
Dreij
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Åse
Å
Mattsson
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Bengt
B
Jernström
Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden.
Ulla
U
Stenius
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000633:toxicity*; D045424:Complex Mixtures / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D018570:Risk Assessment
D002273:Carcinogens; D045424:Complex Mixtures; D011084:Polycyclic Aromatic Hydrocarbons; D004247:DNA
Benzo[a]pyrene; Cancer; Complex mixtures; Polycyclic aromatic hydrocarbons; Risk assessment