Comparison of CoMFA models for Salmonella typhimurium TA98, TA100, TA98 + S9 and TA100 + S9 mutagenicity of nitroaromatics.

Meiyun Fan, C. Byrd, C. M. Compadre, R. L. Compadre

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Comparative Molecular Field Analysis (CoMFA) was applied to a comprehensive data set of heterogeneous nitroaromatics tested in Salmonella typhimurium TA98 and TA100 with and without S9 microsomal activation. The four CoMFA models developed agree with postulated mechanisms of mutagenicity, and explain over 70% of the corresponding mutagenic variance The standard deviation coefficient contours common in the four models included high electronic density regions equivalent to C4-C5 in the pyrene ring, and an electron deficient site equivalent to C6. These areas are associated with high mutagenicity. Electron deficient areas may be related with the nitroreductive bioactivation of nitroaromatics. Electron rich sites may be involved with oxidative mechanisms analogous to the bioactivation pathway of polycyclic aromatic hydrocarbons. The contribution of steric factors to mutagenicity follows the order TA98 + S9 > TA98 > TA100 + S9 > TA100. The models indicated that increasing bulk perpendicular to the aromatic plane would decrease mutagenicity, but increasing the aromatic ring system along a region corresponding to C6-C7 in 1-nitropyrene would increase mutagenicity.

Original languageEnglish (US)
Pages (from-to)187-215
Number of pages29
JournalSAR and QSAR in environmental research
Volume9
Issue number3-4
DOIs
StatePublished - Jan 1 1998

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Salmonella
Salmonella typhimurium
1-nitropyrene
Electrons
Polycyclic Aromatic Hydrocarbons
Pyrene
Polycyclic aromatic hydrocarbons
Chemical activation

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Molecular Medicine
  • Drug Discovery

Cite this

Comparison of CoMFA models for Salmonella typhimurium TA98, TA100, TA98 + S9 and TA100 + S9 mutagenicity of nitroaromatics. / Fan, Meiyun; Byrd, C.; Compadre, C. M.; Compadre, R. L.

In: SAR and QSAR in environmental research, Vol. 9, No. 3-4, 01.01.1998, p. 187-215.

Research output: Contribution to journalArticle

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