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Evaluation of Micronuclei and DNA Damage in B6C3F1 Male Mice Administered 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone by Intraperitoneal Injection

Evaluation of Micronuclei and DNA Damage in B6C3F1 Male Mice Administered 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone by Intraperitoneal Injection

Principal Investigators: Jeffrey Davis and Juan Crespo-Barreto

Funding Mechanism:  Research Contract

ID number:  HHSF223201510034I

Award Date: 7/12/2017

Institution:  Integrated Laboratory System

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is on FDA’s published list of harmful and potentially harmful constituents (HPHCs) in smokeless tobacco products and tobacco product smoke. NNK is a strong lung carcinogen, causing lung tumors in a variety of laboratory animals, including mice. This study will evaluate the gene toxicity potential of NNK in live animals using a micronucleus and comet assay study. Researchers will treat mice with NNK or a positive control chemical and evaluate the animals for genetic toxicity. Researchers will assign five male mice to each one of three experimental groups (NNK, positive control, and negative control) and will administer the respective treatments for three consecutive days. After exposure, they will collect blood and bone marrow cells for micronuclei frequency assessment (chromosomal abnormalities that serve as surrogates for carcinogenic potential) and liver, lung, and bone marrow for DNA damage assessment. Study findings will provide information regarding the genotoxic and chromosomal damage profile of NNK and the carcinogenicity mode of action for NNK.