Nucleophilic targets in carcinogenesis, mutagenesis and chemotherapy of cancer.
A hypothesis is suggested, which emphasizes the role in carcinogenesis of the attack on low molecular nucleophilic substances (LMN) by electrophilic agents - chemical carcinogens, phisical factors, and antitumor alkylating agents. The significance of the degree of nucleophilicity (electronic charge, order of bonds, index of valence) as a locus minoris resistentiae of the LMN in the electrophilic attack on the latter is emphasized as well as the probable role of the hydrogenated pteridines in influencing carcinogenesis by means of ascorbate, tocopherol, SH-containing compounds etc. In support of this hypothesis the preference of electrophilic agents (derivatives of nitrogen mustard and nitrosoureas) for the places with highest degree of nucleophilicity as targets, in experiments in vitro with nucleic bases and pteridines is emphasized.
D000477:Alkylating Agents; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D005492:Folic Acid / Q000378:metabolism*; D007700:Kinetics; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D011789:Quantum Theory; D013056:Spectrophotometry, Ultraviolet; D013763:Tetrahydrofolates / Q000378:metabolism*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D002273:Carcinogens; D009607:Nitrosourea Compounds; D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D005492:Folic Acid