Affordable Access

Determinants of nucleic acid adduct formation.

Authors
  • Scribner, J D
Type
Published Article
Journal
National Cancer Institute monograph
Publication Date
Dec 01, 1981
Issue
58
Pages
173–181
Identifiers
PMID: 7341975
Source
Medline
License
Unknown

Abstract

Although N-aryl- or N-acetyl-N-arylnitrenium ions are considered the reactive species in the attack of many aromatic amines or amides on biologic macromolecules, a coherent picture explaining the variety of reactions of the ultimate carcinogens from which they are derived has not been established. Self-consistent field-molecular orbital calculations were used to attempt to understand the reactions of 3 ultimate carcinogens in the aromatic amine class. The MINDO/3 calculations for the cations resulting from loss of acetate from 3-acetoxyxanthine, N-acetoxy-2-fluorenylacetamide (N-AcO-2-FAA) and N-acetoxy-4-acetamidostilbene show that these cations are unlikely to exist in a triplet state, contrary to experimental data which could be interpreted otherwise. Iterative extended Hückel theory calculations for these cations show that the reactions which suggested a triplet state may be explained on the basis of hard/soft-acid/base theory. Electrostatic potential maps combined with frontier orbital theory suggest a coherent explanation for the variety of reactions of N-AcO-2-FAA. The use of the polyelectronic perturbation theory has previously been shown to predict correctly the major product of reaction between guanosine and 5 ultimate carcinogens. I have shown here that the unmodified theory (using Hückel molecular orbital theory) further predicts the major product of reaction between DNA and N-hydroxy-2-naphthyl-amine, but that it predicts secondary products incorrectly.

Report this publication

Statistics

Seen <100 times