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. Author manuscript; available in PMC: 2014 Aug 15.
Published in final edited form as: Int J Cancer. 2013 Mar 9;133(4):961–971. doi: 10.1002/ijc.28092

Figure 2. Proposed model of PhIP metabolism and DNA adduct formation in human prostate in relation to inflammation, atrophy, and cancer risk.

Figure 2

Depending on inherited susceptibility and level of dietary intake, PhIP exposure elicits a variable inflammatory response. A strong response (left side of figure) may dampen the expression of CYP1A enzymes, leading to accumulation of fewer active PhIP metabolites (N2-hydroxy-PhIP), and subsequently lower levels of DNA adducts; a strong inflammatory response would also accelerate atrophy of prostate glandular cells, but not necessarily lead to carcinogenesis. Alternatively, a weak inflammatory response to PhIP exposure (right side of figure) may result in higher CYP1A activity levels, generation of more active PhIP metabolites, and subsequently higher levels of DNA adducts, but the progression of cellular atrophy would not be as rapid. A late elevated inflammatory response coupled with high levels of DNA adducts could incite prostate carcinogenesis.