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A mixture of Persistent Organic Pollutants (POPs) and Azoxymethane (AOM) show potential synergistic effects on intestinal tumorigenesis in the A/J Min/+ mouse model

Hansen, K.E.Aa, Johanson, S.M., Steppeler, C., Sødring, M., Østby, G.C., Berntsen, H.F., Zimmer, K.E., Aleksandersen, M., Paulsen, J.E., Ropstad, E.
Chemosphere 2019 v.214 pp. 534-542
animal models, azoxymethane, breasts, carcinogenesis, carcinogens, carcinoma, colon, colorectal neoplasms, diet, dose response, foods, histopathology, humans, liver, mice, microscopy, persistent organic pollutants, small intestine, subcutaneous injection, synergism, testes
A multitude of cancer types, including breast, testicular, liver and colorectal cancer, have associations with exposure to Persistent Organic Pollutants (POPs). The present study aimed to investigate whether a mixture of POPs could affect intestinal tumorigenesis in the A/J Min/+ mouse, a model for human colorectal cancer (CRC). Pollutants were selected for their presence in Scandinavian food products and the mixture was designed based on defined human estimated daily intake levels. Mice were exposed through the diet, at control, low and high mixture concentrations, for 10 weeks. In a separate experiment, mice also received one subcutaneous injection of Azoxymethane (AOM) to explore whether this carcinogenic compound influenced the effect of the POPs. Intestinal tumorigenesis was examined by surface microscopy and histopathology. Moderate and dose-dependent increases in tumorigenesis were observed after dietary POP exposure. The AOM treatment alone stimulated the growth of colonic lesions, but did not increase the formation of new lesions. Combined AOM treatment and POP exposure demonstrated a synergistic effect on lesion formation in the colon, and to a lesser extent in the small intestine. This synergy was also evident by an increased number of malignant colonic tumors (carcinomas). In conclusion, the study shows that a mixture of POPs interacted synergistically with a known carcinogen (AOM), causing increased intestinal tumorigenesis in the A/J Min/+ mouse model.