Mdm2 as a sensitive and mechanistically informative marker for genotoxicity induced by Benzo[a]pyrene and Dibenzo[a, l]pyrene

Toxicological Sciences

Volumn 102, Issue 2, 2008, Pages 232-240

  Malmlöf, Maria ^a   Pääjärvi, Gerd ^a   Högberg, Johan ^a   Stenius, Ulla ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Benzo a pyrene; Dibenzo a,l pyrene; Mdm2; p53; PAH

Indexed keywords

ACROLEIN; BENZO[A]PYRENE; CAFFEINE; DIBENZO[A,L]PYRENE; ETOPOSIDE; FLUOROURACIL; HISTONE H2AX; MITOMYCIN C; POLYCYCLIC AROMATIC HYDROCARBON; PROTEIN MDM2; PROTEIN P53; SMALL INTERFERING RNA;

ARTICLE; BIOLOGICAL MONITORING; CHROMATIN; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; GENOTOXICITY; HUMAN; HUMAN CELL; MUTAGENICITY; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION;

BENZO(A)PYRENE; BENZOPYRENES; CARCINOGENS; CELL LINE, TUMOR; CHROMATIN; DNA DAMAGE; DNA, NEOPLASM; DOSE-RESPONSE RELATIONSHIP, DRUG; GENETIC MARKERS; HUMANS; MUTAGENS; PHOSPHORYLATION; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS C-MDM2; RNA, SMALL INTERFERING; TRANSFECTION;

EID: 40949151502     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfm305     Document Type: Article

References (42)

1. Al Rashid, S. T., Dellaire, G., Cuddihy, A., Jalali, F., Vaid, M., Coackley, C., Folkard, M., Xu, Y., Chen, B. P., Chen, D. J., et al. (2005). Evidence for the direct binding of phosphorylated p53 to sites of DNA breaks in vivo. Cancer Res. 65, 10810-10821.
2. Alt, J. R., Bouska, A., Fernandez, M. R., Cemy, R. L., Xiao, H., and Eischen, C. M. (2005). Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. J. Biol. Chem. 280, 18771-18781.
3. Balass, M., Kalef, E., Maya, R., Wilder, S., Oren, M., and Katchalski-Katzir, E. (2002). Characterization of two peptide epitopes on Mdm2 oncoprotein that affect p53 degradation. Peptides 23 1719-1725.
4. Bartkova, J., Horejsi, Z., Koed, K., Kramer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., et al. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864-870.
5. Cohen, S. M., Meek, M. E., Klaunig, J. E., Patton, D. E., and Fenner-Crisp, P. A. (2003). The human relevance of information on carcinogenic modes of action: Overview. Crit. Rev. Toxicol. 33 581-589.
6. Committee on Carcinogenicity of Chemical in Food, C.P.A.T.E. (2004). Guidance on a Strategy for the Risk Assessment of Chemical Carcinogens Committee on Carcinogenicity, London, UK.
7. Courter, L. A., Musafia-Jeknic, T., Fischer, K., Bildfell, R., Giovanini, J., Pereira, C., and Baird, W. M. (2007). Urban dust particulate matter alters PAH-induced carcinogenesis by inhibition of CYP1A1 and CYP1B1. Toxicol. Sci. 95, 63-73.
8. Doman, D., Shimizu, H., Mah, A., Dudhela, T., Eby, M., O'Rourke, K., Seshagiri, S., and Dixit, V. M. (2006). ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage. Science 313, 1122-1126.
9. Dreij, K., Seidel, A., and Jernstrom, B. (2005). Differential removal of DNA adducts derived from anti-diot epoxides of dibenzo[a,1]pyrene and benzo[a]pyrene in human cells. Chem. Res. Toxicol. 18, 655-664.
10. Feng, Z., Hu, W., Hu, Y., and Tang, M. S. (2006). Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc. Natl. Acad. Sci. U.S.A. 103, 15404-15409.
11. Finnberg, N., Silins, I., Stenius, U., and Hogberg, J. (2004). Characterizing the role of MDM2 in diethylnitrosamine induced acute liver damage and development of pre-neoplastic lesions. Carcinogenesis 25, 113-122.
12. Ganguli, G., and Wasylyk, B. (2003). p53-independent functions of MDM2. Mol. Cancer Res. 1, 1027-1035.
13. Hamstra, D. A., Bhojani, M. S., Griffin, L. B., Laxman, B., Ross, B. D., and Rehemtulla, A. (2006). Real-time evaluation of p53 oscillatory behavior in vivo using bioluminescent imaging. Cancer Res. 66 7482-7489.
14. Hoshi, M., Morimura, K., Wanibuchi, H., Wei, M,, Okochi, E., Ushijima, T., Takaoka, K., and Fukushima., S. (2004). No-observed effect levels for carcinogenicity and for in vivo mutagenicity of a genotoxic carcinogen. Toxicol. Sci. 81, 273-279.
15. Inoue, T., Geyer, R. K., Yu, Z. K., and Maki, C. G. (2001). Downregulation of MDM2 stabilizes p53 by inhibiting p53 ubiquitination in response to specific alkylating agents. FEBS Lett. 490, 196-201.
16. Jenkins, G. J., Doak, S. H., Johnson, G. E., Quick, E., Waters, E. M., and Parry, J. M. (2005). Do dose response thresholds exist for genotoxic alkylating agents? Mutagenesis 20, 389-398.
17. Knasmuller, S., Parzefall, W., Sanyal, R., Ecker, S., Schwab, C., Uhl, M., Mersch-Sundermann, V., Williamson, G., Hietsch, G., et al. (1998). Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens. Mutat. Res. 402, 185-202.
18. Krewski, D., Acosta, D., Andersen, M., Anderson, H., Bailar, J., III, Boekelheide, K., Brent, R., Chamley, G., Cheung, V., Green, S., et al. (2007). Toxicity testing in the twenty-first century: A vision and a strategy. Report in brief. The National Academies of Sciences
19. Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., and Sharpless, N. E. (2004). Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299-1307.
20. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., 3rd, Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., et al. (2007). ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166.
21. Maya, R., and Oren, M. (2000). Unmasking of phosphorylation-sensitive epitopes on p53 and Mdm2 by a simple Western-phosphatase procedure. Oncogene 19, 3213-3215.
22. Mayo, L. D., Seo, Y. R., Jackson, M. W., Smith, M. L., Rivera Guzman, J., Korgaonkar, C. K., and Donner, D. B. (2005). Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J. Biol. Chem. 280, 25953-25959.
23. Meulmeester, E., Pereg, Y., Shiloh, Y., and Jochemsen, A. G. (2005). ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle 4, 1166-1170.
24. Oren, M. (2003). Decision making by p53: Life, death and cancer. Cell Death Differ. 10, 431-442.
25. Paajarvi, G., Jemström, B., Seidel, A., and Stenius, U. (2004). Exposure of mammalian cells to diol epoxides from benzo[a]pyrene and dibenzo[al]pyrene and effects on Mdm2 and p53. Polycyclic Aromatic Compounds 24, 537-548.
26. Paajarvi, G., Jernstrom, B., Seidel, A., and Stenius, U. Anti-diol epoxide of benzo[a]pyrene induces transient Mdm2 and p53 Ser15 phosphorylation, while anti-diol epoxide of dibenzo[al]pyrene induces a nontransient p53 Ser15 phosphorylation. Mol. Carcinog. (in press).
27. Paajarvi, G., Roudier, E., Crisby, M., Hogberg, J., and Stenius, U. (2005). HMG-CoA reductase inhibitors, statins, induce phosphorylation of Mdm2 and attenuate the p53 response to DNA damage. FASEB J. 19 476-478.
28. Rebbaa, A., Zheng, X., Chu, F., and Mirkin, B. L. (2006). The role of histone acetylation versus DNA damage in drug-induced senescence and apoptosis. Cell Death Differ. 13, 1960-1967.
29. Roe, J. S., Kim, H., Lee, S. M., Kim, S. T., Cho, E. J., and Youn, H. D. (2006). p53 stabilization and transactivation by a von Hippel-Lindau protein. Mol. Cell 22, 395-405.
30. Ross, J. A., Nelson, G. B., Wilson, K. H., Rabinowitz, J. R., Galati, A., Stoner, G. D., Nesnow, S., and Mass, M. J. (1995). Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer Res. 55, 1039-1044.
31. Roudier, E., Mistafa, O., and Stenius, U. (2006). Statins induce mammalian target of rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs. Mol. Cancer Ther. 5, 2706-2715.
32. Saito, S., Yamaguchi, H., Higashimoto, Y., Chao, C., Xu, Y., Fomace, A. J., Jr, Appella, E., and Anderson, C. W. (2003). Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J. Biol. Chem. 278, 37536-37544.
33. Sarkaria, J. N., Busby, E. C., Tibbetts, R. S., Roos, P., Taya, Y., Kamitz, L. M., and Abraham, R. T. (1999). Inhibition of ATM and ATR kit activities by the radiosensitizing agent, caffeine. Cancer Res. 59, 4375-4382.
34. Shinozaki, T., Nota, A., Taya, Y., and Okamoto, K. (2003). Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export. Oncogene 22, 8870-8880.
35. Silins, I., Stenius, U., and Hogberg, J. (2004). Induction of preneoplastic rat liver lesions with an attenuated p53 response by low doses of diethylnitrosamine. Arch. Toxicol. 78, 540-548.
36. Staal, Y. C., Hebels, D. G., van Herwijnen, M. H., Gottschalk, R. W., van Schooten, F. J., and van Delft, J. H. (2007). Binary PAH-mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation. Carcinogenesis 28 2632-2640.
37. Stommel, J. M., and Wahl, G. M. (2005). A new twist in the feedback loop: Stress-activated MDM2 destabilization is required for p53 activation. Cell Cycle 4, 411-417.
38. Toyooka, T., and Ibuki, Y. (2005). Co-exposure to benzo[a]pyrene and UVA induces phosp horylation of histone H2AX. FEBS Lett. 579, 6338-6342.
39. Valentin-Severin, I, Thybaud, V., Le Bon, A. M., Lhuguenot, J. C., and Chagnon, M. C. (2004). The autoradiographic test for unscheduled DNA synthesis: A sensitive assay for the detection of DNA repair in the HepG2 cell fine. Mutat. Res. 559, 211-217.
40. White, D. E., Talbott, K. E., Arva, N. C., and Bargonetti, J. (2006). Mouse double minute 2 associates with chromatin in the presence of p53 and is released to facilitate activation of transcription. Cancer Res. 66, 3463-3470.
41. Yoon, J. H., Besaratinia, A., Feng, Z., Tang, M. S., Amin, S., Luch, A., and Pfeifer, G. P. (2004). DNA damage, repair, and mutation induction by (+)-Syn and (-)-anti-dibenzo[a,1l]pyrene-11,12-diol-13,14-epoxides in mouse cells. Cancer Res. 64, 7321-7328.
42. Yu, Z., Loehr, C. V., Fischer, K. A., Louderback, M. A., Krueger, S. K., Dashwood, R. H., Kerkvliet, N. I., Pereira, C. B., Jennings-Gee, J. E., Dance, S. T., et al. (2006). In utero exposure of mice to dibenzo[a,1]pyrene produces lymphoma in the offspring: Role of the aryl hydrocarbon receptor. Cancer Res. 66, 755-762.