Preview

Proceedings of the National Academy of Sciences of Belarus, Chemical Series

Advanced search

Evaluation of the expression and catalytic activity of cytochrome P450 isoenzymes in cancer cell line A549

Abstract

The contribution of monooxygenase component in carcinogenic activation of a key procarcinogenic derivative of benzo(a) pyrene - 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 has been evaluated. It has been shown that the contribution of monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds with the relatively low level of constitutive expression of CYP1A1 and CYP1B1. When cells are exposed to 20-methylcholanthrene, monooxygenase component in carcinogenic activation of 7,8-benzo(a)pyrenediol has reached 25 %. Moreover, 90 % is accounted for a "complete" carcinogen - diolepoxide-2. As 20-methylcholanthrene is a polycyclic aromatic compound and exists with a benzo(a) pyrene in the tobacco smoke, this suggests a whole pool of polycyclic aromatic hydrocarbons entering the organism may significantly affect not only the level but also the direction of carcinogenic PAH activation of individual compounds.

About the Authors

A. G. Sysa
Институт биоорганической химии НАН Беларуси
Belarus


O. V. Panibrat
Институт биоорганической химии НАН Беларуси
Belarus


A. S. Babenko
РНПЦ онкологии и медицинской радиологии им. Н. Н. Александрова МЗ Беларуси
Belarus


P. S. Shabunya
Институт биоорганической химии НАН Беларуси
Belarus


S. A. Fatykhova
Институт биоорганической химии НАН Беларуси
Belarus


P. A. Kiselev
Институт биоорганической химии НАН Беларуси
Belarus


References

1. De Montellano O., Paul R. // Future Med. Chem. 2013. Vol. 5(2). P. 213-228.

2. Пономаренко Т. М., Сычёв Д .А., Чикало А. О., Бердникова Н. Г., Кукес В. Г. // Фармакокинетика и фармакодинамика. 2012. № 1. С. 25-28.

3. Ляхович В. В., Цырлов И. Б. / Индукция ферментов метаболизма ксенобиотиков. М.: Наука, 1981.

4. Кобляков В. А. / Цитохромы семейства Р-450 и их роль в активации проканцерогенов.М.:ВИНИТИ, 1990.

5. Zhang Li, Jin Yi, Huang M., Penning T. M. // Pharmacol. 2012. Vol. 3. P. 1-12.

6. De Montellano O., Paul R. Cytochrome P450: structure, mechanism, and biochemistry. 3rd edition. New York: Kluwer Academic/Plenum Publishers, 2005.

7. Handschin C., Meyer U. // Pharmacol. Rev. 2003. Vol. 55. P. 649-673.

8. Hukkanen J., Pelkonen O., Hakkola J., Raunio H. // Crit. Rev. Toxicol. 2002. Vol. 32(5). P. 391-411.

9. Castell J. V., Teresa D. M., Gomez-Lechon M. J. // Exp. Toxicol. Pathol. 2005. Vol. 57. P. 189-204.

10. Foster K. A. Exp. Cell. Res. 1998. Vol. 243. P. 336-359.

11. Hukkanen J., Lassila A., Paivarinta K., Valanne S., Sarpo S., Hakkola J., Pelkonen O., Raunio H. // Am. J. Respir. Cell. Mol. Biol. 2000. Vol. 22. P. 360-366.

12. Hitoshi K., Katoh M., Suzuki T., Ando Y., Nadai M. // Drug. Metab. Dispos. 2012. Vol. 40. N 3. P. 579-587.

13. Newland N., Baxter A., Hewitt K., Minet E. // Toxicol In Vitro. 2011. Vol. 25(4). P. 922-929.

14. Conney A. H. // Cancer Res. 1982. Vol.42. P. 4875-4917.

15. IARC-Monographs. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. 32, Polynuclear Aromatic Compounds, Pt. 1, Chemical, Environmental and Experimental Data, IARC, Lyon, France, 1983.

16. Conney A. H., Chang R. L., Jerina D. M., Wei S. J. C. // Drug. Metab. Rev. 1994. Vol. 26. P. 125-163.

17. Livak K. J., Schmittgen T. D. // Methods. 2001. Vol. 25. N 4. P. 402-408.

18. Tsuchiya Y., Nakajima M., Itoh S., Iwanari M., Yokoi T. // Toxicol. sci. 2003. Vol. 72. P. 253-259.

19. Hukkanen, J., Lassila A., Paivarinta K., Valanne S., Sarpo S., Hakkola J., Pelkonen O., Raunio H. // Am. J. Respir. Cell. Mol. Biol. 2000. Vol. 22. P. 360-366.


Review

Views: 435


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1561-8331 (Print)
ISSN 2524-2342 (Online)