Related Experiment Video
Updated: Sep 28, 2026

Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment
Published on: June 28, 2018
Carcinogenic induction directs the selection of allelic losses in mouse lung tumorigenesis
Christopher R Herzog1, Theodora R Devereux, Brian Pittman
1American Health Foundation, Valhalla, New York 10595, USA. cherzog@ahf.org
Abstract:
Recent evidence suggests that genome-wide allelic imbalances are inducible by carcinogens and may occur as cells adapt to carcinogenic exposure during tumorigenesis. We investigated the role of carcinogenic exposure on global and selected loss of heterozygosity (LOH) during mouse lung adenocarcinogenesis. Tumor induction by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or vinyl carbamate (VC) resulted in a significant overall increase in the number of chromosomes affected by LOH per tumor when compared with spontaneous lung tumors. Allelic loss on chromosome 12 occurred at a frequency of 35% and 40% in NNK- and VC-induced tumors, respectively, compared with 8.3% in spontaneous tumors (P < 0.01). In contrast, spontaneous lung adenocarcinomas displayed LOH on chromosome 4 at a frequency of 77%, whereas a frequency of only 36% (P < 0.001) was observed in tumors induced by NNK. Sixty-four percent of the VC-induced tumors displayed LOH on chromosome 4. In addition, allelic losses on chromosomes 12 and 14 were significantly associated with an increase in chromosomal instability, suggesting that genes inactivated on these chromosomes may contribute to this effect. The results from this study demonstrate that genotoxic carcinogens increase chromosome instability, as evidenced by a significant increase in global LOH frequency, and significantly alter the selection of chromosomal alterations during lung tumor development.
Related Concept Videos
Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Mutagenicity and Carcinogenicity
In-vitro Mutagenesis (Gene Knockouts)
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...

