DNA adducts in experimental cancer research.
The role of DNA adducts in the initiation of cancer is scrutinized in this presentation. Work on the activation of oncogenes, particularly on ras, has provided new evidence to link DNA adducts and tumour formation. Polycyclic hydrocarbons and nitroso compounds can cause activation of ras oncogenes through a defined point mutation. The properties of two DNA binding agents, styrene oxide and cisplatin are discussed. Styrene oxide is a versatile electrophile causing numerous adducts; cisplatin has a high specificity towards guanine-N-7 and cross-link formation. Finally, the relation of specific adducts to carcinogenic potency as defined by TD50 values is investigated. For small alkyl groups, O-alkylation of bases correlates with potency but among others, particularly the bulky carcinogens, 7-alkylguanines appear as correlates of potency. Most such potent agents forming 7-alkylguanines induce depurination and imidazole ring-opening.
D000478:Alkylation; D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism; D005786:Gene Expression Regulation; D006151:Guanosine / Q000378:metabolism; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics*; D009857:Oncogenes; D011083:Polycyclic Compounds / Q000378:metabolism
D002273:Carcinogens; D004273:DNA, Neoplasm; D004852:Epoxy Compounds; D011083:Polycyclic Compounds; D006151:Guanosine; D004247:DNA; C013690:styrene oxide; D002945:Cisplatin