Alkylation of inorganic oxo compounds and insights on preventing DNA damage.
Metabolism of food- and tobacco-borne procarcinogens results in the exposure of DNA to toxic alkylating agents. These assaults can bring about DNA alkylation damage, mutations, and cancer. Dietary inorganic compounds such as selenium and vanadium are known to prevent cancer, possibly by reacting directly with alkylating agents, thereby preventing DNA damage. To understand potential interactions between oxo species and alkylating toxins, we reacted a series of alkylating agents with varied classes of oxo compounds (i.e., vanadates, selenate, phosphate, sulfate, acetate, nitrate, and nitrite). A new organic-soluble selenate, [(C6H5)4P]3(O3SeOCH2OSeO3)(HSeO4), was synthesized and characterized for these studies. Vanadates were found to convert ethylating agents into ethanol, whereas other anions formed esters upon alkylation. General trends show that oxo anions of the greatest charge density were the most reactive. These studies suggest that the design of new compounds for cancer prevention should incorporate reactive oxo groups with high anionic charge density.
Hamilton
Elizabeth E
EE
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
Fanwick
Phillip E
PE
Wilker
Jonathan J
JJ
D000085:Acetates / Q000737:chemistry; D000477:Alkylating Agents / Q000737:chemistry*; D000478:Alkylation; D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D004249:DNA Damage; D009566:Nitrates / Q000737:chemistry; D009573:Nitrites / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D064586:Selenic Acid; D018036:Selenium Compounds / Q000737:chemistry; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry; D014638:Vanadates / Q000737:chemistry
D000085:Acetates; D000477:Alkylating Agents; D009566:Nitrates; D009573:Nitrites; D010710:Phosphates; D018036:Selenium Compounds; D013431:Sulfates; D014638:Vanadates; D004247:DNA; D064586:Selenic Acid