Recent Advances in In Vivo Genotoxicity Testing: Prediction of Carcinogenic Potential Using Comet and Micronucleus Assay in Animal Models

Abstract

Genotoxic events have been known as crucial step in the initiation of cancer. To assess the risk of cancer, genotoxicity assays, including comet, micronucleus (MN), chromosomal aberration, bacterial reverse, and sister chromatid exchange assay, can be performed. Compared with in vitro genotoxicity assay, in vivo genotoxicity assay has been used to verify in vitro assay result and definitely provide biological significance for certain organs or cell types. The comet assay can detect DNA strand breaks as markers of genotoxicity. Methods of the in vivo comet assay have been established by Japanese Center for the Validation of Alternative Methods (JaCVAM) validation studies depending on tissue and sample types. The MN can be initiated by segregation error and lagging acentric chromosome fragment. Methods of the in vivo MN assay have been established by Organization for Economic Co-operation and Development (OECD) test guidelines and many studies. Combining the in vivo comet and MN assay has been regarded as useful methodology for evaluating genetic damage, and it has been used in the assessment of potential carcinogenicity by complementarily presenting two distinct endpoints of the in vivo genotoxicity individual test. Few studies have investigated the quantitative relation between in vivo genotoxicity results and carcinogenicity. Extensive studies emphasizes that positive correlation is detectable. This review summarizes the results of the in vivo comet and MN assays that have investigated the genotoxicity of carcinogens as classified by the International Agency for Research on Cancer (IARC) carcinogenicity database. As a result, these genotoxicity data may provide meaningful information for the assessment of potential carcinogenicity and for implementation in the prevention of cancer.

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

“…Its quantification is usually recommended in genotoxic test batteries due to the fact that it is a relatively easy and economical assay and because of its known high efficiency to show chromosome damage. 19,20) Our study revealed a capacity of the tested antidepressant to increase the number of micronuclei in recently formed erythrocytes as shown in the acute assay, where bone marrow damage should have occurred 1-2 d prior to sampling. 21) In this assay, a significant elevation of MNPE was observed with the three tested doses.…”

Combinations of genotoxic tests for the evaluation of group 1 IARC carcinogens

“…With the advancement in the field of genotoxicology, several tests were added to the existing list and an approach is being made to find good combinations of test, which provide better sensitivity as well as specificity. Studies have also shown that different combinations of Ames, in vivo MN, in vivo CA and CMT assay increases the sensitivity of carcinogen detection (Kang et al, ; Kim & Margolin, ; Morita et al, ; Sasaki et al, ). The combination of the Ames test and in vivo MN test was found effective in the detection of human genotoxic carcinogen (Shelby & Zeiger, ).…”

“…The concept of combining the MN and CMTs into one study has only recently found its way into the scientific literature (Recio, Hobbs, Caspary, & Witt, ; Vasquez, ). Kang et al () used a combination of in vivo CMT and MN test to assess the genotoxicity of International Agency for Research on Cancer (IARC) carcinogen.…”

Comet assay: an essential tool in toxicological research

“…They highlighted that the comet assay can be used to assess the genotoxicity of a great number of chemicals, such as contaminants, pesticides, food contact materials or food additives. Furthermore, the comet assay might help to predict the carcinogenic potential of chemicals (Kang et al 2013).…”