Prostate Cancer Genetic Toxicology
Prostate cancer genetic toxicology may have an endogenous or exogenous origin: (i) generation of 2- or 4-hydroxy metabolites of 17-estradiol (E2) via biotransforming enzymes including the phase I cytochrome P450 (CYP) isoform CYP1B1 ultimately giving rise to DNA damage or (ii) bio-activation by phase I metabolism and/or phase II metabolism of candidate causative agents of environmental and/or dietary origin to reactive metabolites that bind covalently to DNA bases.
There are two established risk factors for prostate cancer, the first being increasing age. However, the second is based on the epidemiological observation that there have been demographic regions of remarkably low prostate cancer incidence primarily in countries of the Far East (e.g., China, India, Japan) compared to levels observed in more Westernized areas (e.g., North/Western Europe, the USA, Australia). Populations that...
KeywordsProstate Cancer Peripheral Zone Reactive Metabolite Prostate Epithelial Cell Prostate Cancer Incidence
- John K, Ragavan N, Pratt MM, Singh PB, Al-Buheissi S, Matanhelia SS, Phillips DH, Poirier MC, Martin FL (2009) Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate. Prostate 69:505–519CrossRefPubMedPubMedCentralGoogle Scholar
- Martin FL, Patel II, Sozeri O, Singh PB, Ragavan N, Nicholson CM, Frei E, Meinl W, Glatt H, Phillips DH, Arlt VM (2010) Constitutive expression of bioactivating enzymes in normal human prostate suggests a capability to activate pro-carcinogens to DNA-damaging metabolites. Prostate 70:1586–1599CrossRefPubMedGoogle Scholar
- Martin FL (2013) Epigenetic influences in the aetiology of cancers arising from breast and prostate: a hypothesised transgenerational evolution in chromatin accessibility. ISRN Oncology 624794Google Scholar
- Singh PB, Ragavan N, Ashton KM, Basu P, Nadeem SM, Nicholson CM, Gopala Krishna RK, Matanhelia SS, Martin FL (2009) Quantified gene expression levels for phase I/II metabolizing enzyme and estrogen receptor levels in benign prostate from cohorts designated as high-risk (UK) versus low-risk (India) for adenocarcinoma at this organ site: a preliminary study. Asian J Androl 12:203–214CrossRefPubMedPubMedCentralGoogle Scholar