COMPLEX NATURE OF THE INFLUENCE OF POLYCYCLIC AROMATIC HYDROCARBONS ON THE METABOLIC PROCESSES AS AN IMPORTANT DETERMINANT OF THEIR CARCINOGENIC ACTIVATION
Abstract
In the article, the contribution of the monooxygenase component to the carcinogenic activation of a key procarcinogenic derivative of benzo(a)pyrene – 7,8-benzo(a)pyrenediol in lung adenocarcinoma cell line A549 was evaluated. It is shown that the contribution of the monooxygenase process under the experimental conditions in A549 cells is only 13 %, which corresponds to a relatively low level of the constitutive expression of CYP1A1 and CYP1B1. The situation changes significantly when cells are exposed to 20-methylcholanthrene. In this case, the monooxygenase component in the 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 that the entry into the body a whole pool of polycyclic aromatic hydrocarbons may significantly affect not only the level but also the direction of the carcinogenic PAH activation of individual compounds.
About the Authors
A. G. SYSA
Институт биоорганической химии НАН Беларуси, Минск
Belarus
Belarus
O. V. PANIBRAT
Институт биоорганической химии НАН Беларуси, Минск
Belarus
Belarus
A. S. BABENKO
РНПЦ онкологии и медицинской радиологии им. Александрова Министерства здравоохранения Республики Беларусь, Минск
Belarus
Belarus
P. S. SHABUNYA
Институт биоорганической химии НАН Беларуси, Минск
Belarus
Belarus
S. A. FATYKHOVA
Институт биоорганической химии НАН Беларуси, Минск
Belarus
Belarus
P. A. KISELEV
Институт биоорганической химии НАН Беларуси, Минск
Belarus
Belarus
References
1. DeMontellano O., Paul R. // Future Med. Chem. 2013. Vol. 5(2). P. 213–228.
2. Пономаренко Т. М., Сычёв Д. А., Чикало А. О. и др. // Фармакокинетика и Фармакодинамика. 2012. № 1. С. 25–28.
3. Ляхович В. В., Цырлов И. Б. Индукция ферментов метаболизма ксенобиотиков. М., 1981. – 239 с.
4. Кобляков В. А. Цитохромы семейства Р-450 и их роль в активации проканцерогенов. М., 1990. – 190 с.
5. Zhang Li, Jin Yi, Huang M., Penning T. M. // Pharmacol. 2012. Vol. 3. P. 1–12.
6. DeMontellano O., Paul R. Cytochrome P450: structure, mechanism, and biochemistry. 3d ed. New York, 2005.
7. Handschin C., Meyer U. // Pharmacol. Rev. 2003. Vol. 55. P. 649–673.
8. Conney A. H. // Cancer Res. 1982. Vol. 42. P. 4875–4917.
9. Foster K. A. // Exp. Cell. Res. 1998. Vol. 243. P. 359–366.
10. Livak K. J., Schmittgen T. D. // Methods. 2001. Vol. 25, N 4. P. 402–408.
11. Hitoshi K., Katoh M., Suzuki T. et al. // Drug. Metab. Dispos. 2012. Vol. 40, N 3. P. 579–587.
12. Tsuchiya Y., Nakajima M., Itoh S. et al. // Toxicol. Sci. 2003. Vol. 72. P. 253–259.
Review
Views: 751
Email this article 