DNA-Damaging Activities of Twenty-Four Structurally Diverse Unsubstituted and Substituted Cyclic Compounds in Embryo-Fetal Chicken Livers

Authors

Tetyana Kobets, New York Medical CollegeFollow
Jian-Dong Duan, New York Medical CollegeFollow
Klaus D. Brunnemann, New York Medical CollegeFollow
Esther Vock
Ulrich Deschl
Gary M. Williams, New York Medical CollegeFollow

Journal Title

Mutation Research

First Page

10

Last Page

24

Document Type

Article

Publication Date

August 2019

Department

Pathology, Microbiology and Immunology

Abstract

DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds were assessed in embryo-fetal chicken livers. Formation of DNA adducts and strand breaks were measured using the nucleotide (32)P-postlabelling (NPL) and comet assays, respectively. Unsubstituted monocyclic benzene, polycyclic fused ring compound naphthalene, covalently connected polycyclic ring compound biphenyl, and heterocyclic ring compound fluorene did not produce DNA damage. Amino-substituted monocyclic compounds, aniline and p-phenylenediamine, as well as polycyclic 1-naphthylamine were also negative. In contrast, carcinogenic monocyclic methyl-substituted anilines: o-toluidine, 2,6-xylidine, 3,4-dimethylaniline, 4-chloro-o-toluidine; 2 methoxy-substituted methylaniline: p-cresidine; 2,4 and 2,6 diamino- or dinitro- substituted toluenes all produced DNA damage. Genotoxic polycyclic amino-substituted 2-naphthylamine, 4-aminobiphenyl, benzidine, methyl-substituted 3,2'-dimethyl-4-aminobiphenyl and 4-dimethylaminoazobenzene as well as amino- and nitro- fluorenes substituted at the 1 or 2 positions also were positive in at least one of the assays. Overall, the DNA damaging activity of cyclic compounds in embryo-fetal chicken livers reflected the type and position of the substitution on the aromatic ring. Additionally, substituted polycyclic compounds exhibited higher DNA-damaging potency compared to monocyclic chemicals. These results are congruent with in vivo findings in other species, establishing chicken eggs as a reliable system for structure-activity assessment of members of groups of related chemicals.

Recommended Citation

Kobets, T., Duan, J., Brunnemann, K., Vock, E., Deschl, U., & Williams, G. (2019). DNA-Damaging Activities of Twenty-Four Structurally Diverse Unsubstituted and Substituted Cyclic Compounds in Embryo-Fetal Chicken Livers. Mutation Research, 844, 10-24. https://doi.org/10.1016/j.mrgentox.2019.06.004