Comparative Investigation of In Vitro Induction of DNA Damage and Micronuclei by Pro-Mutagens in Human-Derived Hepatoma HepG2 Cells

Authors: Kawaguchi S , Okutani S , Yamamoto A , Nakamura T and Sasaki YF

DOI: 10.23880/act-16000324

Volume 10, Issue 1

Abstract

It is important to know whether the DNA initial lesions are repaired or derive into chromosome aberration, gene mutation and/or cell death to discuss chemical carcinogenicity. To know whether DNA damage detected by the comet assay is repaired or fixed, the results of micronucleus (MN) test was compared to those of the comet assay in HepG2 cells. HepG2 cells were exposed to 38 pro-mutagens for 4 h followed by the cultivation for 24 h with cytochalasin B and the results were compared to those of the comet assay shown in our previous study where HepG2 cells were exposed to same 38 pro-mutagens for 4 h followed by immediate sampling. Among 38 pro-mutagens studied, 35 were positive in the comet assay and 22 were positive in the MN test. Since for 7 pro-mutagens, the lowest comet-positive concentration was higher than MN-positive concentration range, it is difficult to declare simply that the detecting ability of the comet assay is superior to that of the MN test. Comet assay-detected DNA damages that were induced by aromatic nitro compounds, azo dyes, heterocyclic amines, and aromatic hydrocarbons having bay structure, and aromatic amines with condensed multiple ring tended to result in cytotoxicity rather than MNs. It was considered that one important factor to decide the fate to produce MNs of comet-detected DNA damages might be whether detected DNA damages are bulky base adducts at non-cytotoxic concentration range and that chemical structures of pro-mutagens are important factor to decide whether induced base adducts are bulky.

Keywords: HepG2 Cells; Comet Assay; Micronuclei; Fate of DNA Damage

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