Seleno-L-Methionine Modulation of Nucleotide Excision DNA Repair Relevant to Cancer Prevention and Chemotherapy

Abstract

Organic selenium compounds are known to prevent certain cancers although mechanisms may be complex. A widely-held view is that selenium compounds can induce apoptosis in cancer cells, or more precisely, in aberrant cells that are undergoing clonal evolution somewhere along the carcinogenesis process. There are at least 20 different selenium compounds, inorganic as well as organic, that have been used in various published studies. Extrapolation between studies should therefore be undertaken with caution. Similarly, it will be important to ascertain the physiological relevance of the selenium concentrations used in some studies. While cancer prevention by selenium is well-established, recently, organic selenium in the form of pure seleno-L-methionine (SeMet) has been used in combination with cancer chemotherapy drugs. SeMet can induce a DNA repair response in some cell types including bone marrow. Cancer cells generally lack a SeMet-inducible DNA repair response. Thus, SeMet appears to selectively regulate a DNA repair pathway and thereby potentially alter responses to cancer chemotherapy drugs. The specific pathway implicated, nucleotide excision DNA repair (NER) is required for repair of cisplatin or carboplatin DNA damage relevant to chemotherapy. Moreover, some studies have implicated NER as a factor in carcinogenesis processes. Thus, the capacity of SeMet to selectively regulate NER may prove useful in both therapeutic and preventive contexts.