A critical assessment of the methodologies to investigate the role of inhibition of apoptosis in rodent hepatocarcinogenesis.
Non-genotoxic carcinogens act by promoting the clonal expansion of preneoplastic cells by directly or indirectly stimulating cell division or inhibiting cell loss in the target organ. The specific mode-of-action (MoA) by which some non-genotoxic carcinogens ultimately cause cancer is not completely understood. To date, there are several proposed MoAs for non-genotoxic carcinogens, and some of these propose inhibition of apoptosis as one of the key events. In general, inhibition of apoptosis is considered a necessary step for cell survival and in theory can occur in combination or in association with other key promotional events, such as cell proliferation, oxidative stress and inhibition of intercellular communication to promote carcinogenesis. However, the evidence supporting the role of inhibition of apoptosis as a necessary step in promoting specific chemically induced tumors is often debated. To address this evidence, we reviewed studies that utilized prototypical nuclear receptor-mediated hepatocarcinogens. Based on this review, it is proposed that the ability to determine the importance of inhibition of apoptosis as a key event in the MoA for tumor promotion is hampered by the limitations of the methods utilized for its detection. This review provides an assessment of the strengths and limitations of the current methodology used for detection of apoptosis and provides suggestions for improving its detection, thereby strengthening the weight of evidence supporting inhibition of apoptosis as a key event in a MoA for tumor promotion.
['Sura|Radhakrishna|R|', 'Settivari|Raja S|RS|', 'LeBaron|Matthew J|MJ|', 'Rowlands|J Craig|JC|', 'Carney|Edward W|EW|', 'Gollapudi|B Bhaskar|BB|']
D000818:Animals D017209:Apoptosis D035843:Biomedical Research D017173:Caenorhabditis elegans D063646:Carcinogenesis D002273:Carcinogens D002450:Cell Communication D045744:Cell Line, Tumor D049109:Cell Proliferation D002478:Cells, Cultured D004195:Disease Models, Animal D006801:Humans D008099:Liver D008113:Liver Neoplasms D015394:Molecular Structure D018384:Oxidative Stress D021281:Quantitative Structure-Activity Relationship
Apoptosis rodent non-genotoxic carcinogens key event hepatocarcinogens