4-Nonylphenol alters estrogen metabolism in FVB/NJ mice after acute and chronic exposures

We were interested in determining the effects of 4-NP on steroid metabolism and mammary cancer formation in FVB/N-TgN(MMTVneu)202Mu1 (MMTVneu) mice susceptible to mammary cancer formation. Therefore, we performed a pilot study with FVB/NJ mice for 7 days to determine our oral dosing regimen and then treated the MMTVneu mice for 32 weeks to determine 4-NP's effects on mammary cancer, P-450s and steroid metabolism. 4-NP increased mammary cancer formation, and also demonstrated significantly different effects on steroid metabolism and P-450 expression in mice treated for 32 weeks compared to mice treated for 7 days. It was observed that nonylphenol increased tumor formation in MMTVneu mice in a manner consistent with its estrogenicity. However, 4-NP was more potent than expected compared to estradiol based on their respective affinities for ERalpha. Altered estradiol metabolism may play a role since 4-nonylphenol increased the production of the estrogenic estradiol metabolites, estriol. However, long-term exposure to 4-NP caused a refractory response on the estrogen metabolism. The mechanism of this response is unknown, but is currently being investigated by other members of the lab. More work needs to be done, but our current data indicates that 4-nonylphenol is a potential risk factor for tumor formation.