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Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

1 Jan 2017Review

Chromosomal aberrations, clastogens vs aneugens

Masayuki Mishima 1,*
Affiliation
Article Info

1 Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, 412-8513, Japan

*Author to whom correspondence should be addressed.

 

Abstract

Current anticancer therapy may be one of the most important exogenous sources of exposure to genotoxic agents in US, Japan, and Europe, where approximately 40–55 percent of the population is diagnosed with cancer at a certain point in their life. This review focuses on recent efforts to integrate a novel biomarker, gamma-H2AX, into anticancer drug screening to classify the mode of action (MoA) for genotoxic outcome into clastogenicity and aneugenicity, a distinction that has considerable impact on risk assessment and control strategy. The emerging biomarker gamma-H2AX is applicable to high throughput assay platforms and is therefore changing in vitro mammalian genotoxicity screening from traditional positive/negative selection to MoA elucidation. Because gamma-H2AX is not only a sensitive biomarker for DNA double strand break but is also induced by apoptosis, the key for successful screening is using additional biomarkers of caspase-3 and/or phosphorylated histone H3 to discriminate between relevant and irrelevant elevation of gamma-H2AX. Establishment of a standard methodology and a consensus threshold for its positive criteria will further support the application of gamma-H2AX to drug screening.

Keywords

  • Aneugen
  • Clastogen
  • Genotoxicity
  • Apoptosis
  • Gamma-H2AX
  • Review

References