This project aimed to investigate potential adverse effects on development tumorogenesis resulting from combined exposure with persistent organic pollutants (POPs), including also perfluorinated compounds (PFC) and mixtures thereof, reflecting natural exposure scenarios. To explore this chain of events we studied the effects of different POPs, alone or in combination. We designed human relevant mixtures of POPs based on human intake and measured blood concentrations. In animal experiements we demonstrated exposure effects on breast development resulting from maternal transfer of POPs to offspring in human relevant concentrations. We could not demonstrate development of breast cancer resulting from exposure, but an increase in colorectal cancer was found in a mouse strain that is genetically predisposed for this cancer type. In vitro studies of mouse lymphocytes revealed a small,but significant increase in DNA damage resulting from POP exposure. Reactive oxygen species were formed in isolated human white blood cells and transformation of syrian hamster embryonic cells, which is indicative of cancer inducing ability. Studies on PFC and the human relevant mixture of POP showed that these compounds disturbed cellular events related to normal development of glandular breast tissue through estrogen independent mechanisms. These events were associated with a disturbance of intercellular communication through gap junctions. It was concluded that POP exposure in human relevant concentrations was associated with effects that potentially can be related to cancer development.
Research on combination effects of persisten organic pollutants (POPs) and methods for a systematic approach are required for an improved risk-assessment of health- and environment damaging chemicals.
This project will investigate potential genotoxicity and tumorogenesis resulting from combined exposure with POPs and mixtures thereof, reflecting natural exposure scenarios.
POPs are capable of generating oxygen radicals in exposed cells and tissues. Combined exposure to mixtures of pollutants forming th ese radicals will lead to increased oxidative stress, which in turn can lead to DNA damage, ultimately resulting in developmental insults, and increased risk of cancer. Certain PFCs have been shown to increase intracellular concentrations of POPs, and thu s might aggravate their adverse effects.
We will apply a multi-tiered approach of increasing complexity, using in vitro cell lines, organotypic models, and in vivo animal studies to investigate environmental pollutant induced oxidative stress, resultin g in oxidative DNA damage during sensitive stages of breast and testis development. Sensitive knock-out (ko) mice models, for initiation of DNA repair of oxidative damage, will be phenotypically characterised during and after life long exposure to mixture s of classical persistent organic pollutants (POPs) and newer perfluorinated compounds (PFCs) starting at conception. We will specifically address increased risks of tumorogenesis, by studying the genotoxic and carcinogenic ability of the compounds in a s ensitive animal model, alone and combined in environmentally relevant mixtures.
The results will contribute to development of product safety and quality guidelines as well as protection of the environment by providing recommendations for policymakers con cerning environmental policy and consumer safety