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Experimental Oral Carcinogenesis Using 4-Nitroquinoline-1-oxide (4-NQO): Creating an Intervention Window for Chemoprevention Studies
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788230
*Corresponding author: (e-mail: manojbmahimkar@gmail.com/mmahimkar@actrec.gov.in).
Abstract
Background: The 4-nitroquinoline-1-oxide (4NQO) mouse model, widely utilized for studying oral carcinogenesis, closely resembles human oral cancer histologically and genetically. Yet, in its conventional methodology, including 16 weeks of continuous carcinogen exposure via drinking water, it presents challenges of elevated toxicity, mortality, and limited potential for chemopreventive interventions.
Materials and Methods: To overcome these limitations, we developed a new/modified 4NQO-induced tumorigenesis protocol where the carcinogen is administered three times a week until the 28th week (experimental endpoint), thus providing a window for potential interventions. We also investigated the effect of two different 4NQO doses (50 and 100 ppm) on tumor yield.
Results: Our results showed no significant differences in tumor numbers and volumes between the conventional and modified treatment settings. However, the animal subjects in the conventional regimen exhibited early weight loss, indicating toxicity. Interestingly, the 50 ppm group exhibited higher median tumor numbers and volumes, likely attributed to reduced toxicity of the dose and improved hydration due to higher water consumption containing 4NQO at the 50 ppm dose. This suggests a potential link between reduced toxicity and increased tumor burden, even though no statistically significant differences were observed between the two doses in the modified setting.
Conclusion: Thus, our modified 4NQO treatment protocol offers the window for chemopreventive/therapeutic interventions without exhibiting toxicity and compromising tumorigenicity, making it a valuable resource for oral carcinogenesis/chemoprevention research.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: manojbmahimkar@gmail.com/mmahimkar@actrec.gov.in).
Abstract
Background: The 4-nitroquinoline-1-oxide (4NQO) mouse model, widely utilized for studying oral carcinogenesis, closely resembles human oral cancer histologically and genetically. Yet, in its conventional methodology, including 16 weeks of continuous carcinogen exposure via drinking water, it presents challenges of elevated toxicity, mortality, and limited potential for chemopreventive interventions.
Materials and Methods: To overcome these limitations, we developed a new/modified 4NQO-induced tumorigenesis protocol where the carcinogen is administered three times a week until the 28th week (experimental endpoint), thus providing a window for potential interventions. We also investigated the effect of two different 4NQO doses (50 and 100 ppm) on tumor yield.
Results: Our results showed no significant differences in tumor numbers and volumes between the conventional and modified treatment settings. However, the animal subjects in the conventional regimen exhibited early weight loss, indicating toxicity. Interestingly, the 50 ppm group exhibited higher median tumor numbers and volumes, likely attributed to reduced toxicity of the dose and improved hydration due to higher water consumption containing 4NQO at the 50 ppm dose. This suggests a potential link between reduced toxicity and increased tumor burden, even though no statistically significant differences were observed between the two doses in the modified setting.
Conclusion: Thus, our modified 4NQO treatment protocol offers the window for chemopreventive/therapeutic interventions without exhibiting toxicity and compromising tumorigenicity, making it a valuable resource for oral carcinogenesis/chemoprevention research.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India