Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

Anna Csiszar^{1

2}, Priya Balasubramanian¹, Stefano Tarantini¹, Andriy Yabluchanskiy^{1

2}, Xin A Zhang³, Zsolt Springo^{1

4}, Doris Benbrook^{2

5}, William E Sonntag^{1

6}, Zoltan Ungvari^{7

8

9

10

11}

Affiliations

¹ Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.
² Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary.
⁵ Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷ Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA. zoltan-ungvari@ouhsc.edu.
⁸ Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. zoltan-ungvari@ouhsc.edu.
⁹ Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary. zoltan-ungvari@ouhsc.edu.
¹⁰ Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary. zoltan-ungvari@ouhsc.edu.
¹¹ Department of Public Health, Semmelweis University, Budapest, Hungary. zoltan-ungvari@ouhsc.edu.

PMID: 31037472
PMCID: PMC6544731
DOI: 10.1007/s11357-019-00064-4

Review

Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

Anna Csiszar et al. Geroscience. 2019 Apr.

. 2019 Apr;41(2):209-227.

doi: 10.1007/s11357-019-00064-4. Epub 2019 Apr 29.

Authors

Affiliations

¹ Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.
² Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary.
⁵ Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁶ Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷ Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA. zoltan-ungvari@ouhsc.edu.
⁸ Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. zoltan-ungvari@ouhsc.edu.
⁹ Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary. zoltan-ungvari@ouhsc.edu.
¹⁰ Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary. zoltan-ungvari@ouhsc.edu.
¹¹ Department of Public Health, Semmelweis University, Budapest, Hungary. zoltan-ungvari@ouhsc.edu.

PMID: 31037472
PMCID: PMC6544731
DOI: 10.1007/s11357-019-00064-4

Abstract

There is significant overlap between the cellular and molecular mechanisms of aging and pathways contributing to carcinogenesis, including the role of genome maintenance pathways. In the field of geroscience analysis of novel genetic mouse models with either a shortened, or an extended, lifespan provides a unique opportunity to evaluate the synergistic roles of longevity assurance pathways in cancer resistance and regulation of lifespan and to develop novel targets for interventions that both delay aging and prevent carcinogenesis. There is a growing need for robust assays to assess the susceptibility of cancer in these models. The present review focuses on a well-characterized method frequently used in cancer research, which can be adapted to study resilience to genotoxic stress and susceptibility to genotoxic stress-induced carcinogenesis in geroscience research namely, chemical carcinogenesis induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). Recent progress in understanding how longer-living mice may achieve resistance to chemical carcinogenesis and how these pathways are modulated by anti-aging interventions is reviewed. Strain-specific differences in sensitivity to DMBA-induced carcinogenesis are also explored and contrasted with mouse lifespan. The clinical relevance of inhibition of DMBA-induced carcinogenesis for the pathogenesis of mammary adenocarcinomas in older human subjects is discussed. Finally, the potential role of insulin-like growth factor-1 (IGF-1) in the regulation of pathways responsible for cellular resilience to DMBA-induced mutagenesis is discussed.

Keywords: Cancer; Carcinoma; DNA repair; Health span; Mutagenesis; Mutation; Tumor.

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Figures

**Fig. 1**
Concept figure illustrating the overlap between mechanisms of aging and mechanisms involved in carcinogenesis. Accordingly, impairment of DNA repair pathways and consequential DNA damage contribute both to impaired organismal stress resilience, accelerating the process of aging and increase susceptibility to carcinogenesis. Investigating DMBA-induced carcinogenesis in rodent models of longevity is a useful approach to understand the underlying mechanisms of both aging and age-related cancer development

See this image and copyright information in PMC

References

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Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

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Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

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