DNA Damage and Cytotoxicity Caused by Nitric Oxide

Nitric oxide-induced mutations in theHPRT gene of human lymphoblastoid TK6 cells and inSalmonella typhimurium

“…The wide variety of DNA damage observed correlates with the observation that nitric oxide induces all six possible base-pair mutations in this system. One of the major pathways for NO to cause DNA damage is reaction with molecular oxygen to form N 2 O 3 , which can react with primary or secondary amines to lead to nitrosative deamination or the formation of mutagenic N-nitrosoamines, respectively [Tannenbaum et al, 1994]. Most of the observed mutations in this study can be explained by deamination mechanisms.…”

“…Guanine, adenine, cytosine, and 5-methylcytosine all contain exocyclic amines, which are subject to nitrosative deamination when exposed to NO. Alternatively, N 2 O 3 can nitrosate secondary amines to form N-nitrosoamines, which are potent alkylating agents, mutagens, and carcinogens [Tannenbaum et al, 1994]. In addition to deamination, nitric oxide causes abasic sites in vivo, leading to DNA single-and double-strand breaks [Tamir et al, 1996a], and can also cause interstrand crosslinking (unpublished data).…”

Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis

“…NO can damage DNA through a variety of different mechanisms that may be cell specific (107). Nitrosation of purines and pyrimidines results in hydrolytic deamination of cytosine to uracil and guanine to xanthine (81,109). GC 3 AT and GC 3 CG transitions (replacement of purine by pyrimidine base or vice versa) are major mutations observed in naked DNA and human cells exposed to NO (127).…”

A new method for monitoring dediazoniation reactions: Simultaneous monitoring of concentration and rates of product formation and loss of starting material for the dediazoniation ofp-methylbenzenediazonium tetrafluoroborate

“…The field remains active [8] because their rich chemistry varies dramatically with experimental conditions [2,4] and because the many reaction pathways are still not completely understood [2,4,5]. Arenediazonium salts are being used to probe interfacial compositions of association colloids [9], as aryl radical sources for synthetic precursors [4,10,11] and their role in DNA arylations [12,13] and DNA deaminations [14] is being explored. A new bonding model [15] based on theoretical calculations that characterizes the C 9 N bond emphasizes a dative bond between an overall, essentially neutral, N 2 group and the positively charged hydrocarbon fragment has been recently proposed.…”