Evidence for an unstable DNA adduct from N-nitroso-N-methylaniline

Journal Article · · Chemical Research in Toxicology; (USA)

DOI:https://doi.org/10.1021/tx00013a003· OSTI ID:6155854

Koepke, S R; Kroeger-Koepke, M B; Michejda, C J ^[1]

---

1. NCI-Frederick Cancer Research Facility, MD (USA)

N-Nitroso-N-methylaniline (NMA) is an esophageal carcinogen in F344 rats. Attempts to detect binding of NMA to DNA or RNA have not been successful. NMA is not mutagenic in the standard Ames bacterial assay, and it did not induce sister chromatid exchanges in mammalian cells. NMA forms the benzenediazonium ion (BDI) during metabolism. This ion has been known to react with aromatic amines, such as adenine, to form triazene coupling products. The purpose of this research was to demonstrate that a triazene adduct, which would be expected to be hydrolytically unstable, was formed by coupling with the adenine residues in DNA. Liver DNA from a rat treated with NMA or from in vitro reactions of BDI with DNA was treated with sodium borohydride. The hydrolysate of the DNA, presumably containing the hydrazine, was treated with 4-(dimethylamino)naphthaldehyde, and the resulting hydrazone was isolated by reverse-phase HPLC using fluorescence detection. The data suggest strongly that NMA forms an unstable triazene adduct with adenine in DNA both vitro and in vivo.

• OSTI ID: 6155854
• Journal Information: Chemical Research in Toxicology; (USA), Journal Name: Chemical Research in Toxicology; (USA) Vol. 3:1; ISSN CRTOE; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
ANILINE
AROMATICS
CARCINOGENS
CHROMATOGRAPHY
DNA ADDUCTS
IN VITRO
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
ORGANIC COMPOUNDS
SEPARATION PROCESSES
SPECTROSCOPY
SYNTHESIS