Identification of Estrogenic and Antiestrogenic Activities ofRespirable Diesel Exhaust Particles by Bioassay-directed Fractionation

다국어 초록 (Multilingual Abstract)

Bioassay-directed fractionation was performed to identify causative chemical groups of DEPs with estrogenic and antiestrogenic activities. Bioassay-directed fractionation consists of a cell bioassay (E-SCREEN) in conjunction with acid-base partitioning (F1 and F2) and silica gel column fractionation of neutral fractions (F3-F7). Crude extract (CE) of DEPs in dichloromethane (DCM) exhibited both estrogenic and antiestrogenic activity. Estrogenic activity of CE and some fractions (F1, F2, F3, F5 and F6) was induced through estrogen receptor (ER)-mediated pathways. In particular, the acid polar fraction (F2) of DEPs, which contains phenols, induced high levels of estrogenic activity compared to other fractions. The estrogenic activity of F2 (610.80 pg-bio-EEQ/g-DEPs) was higher than that of the total estrogenic activity of CE (222.22 pg-bio-EEQ/g-DEPs). This result indicates that the estrogenic activity induced by causative estrogenic fraction (F2) may be antagonized by unidentified chemicals in DEPs. On the other hand, non-polar fractions (F3 and F4) of DEPs include aliphatic and chlorinated hydrocarbon, polyaromatic hydrocarbons, and their alkyl derivatives, which play an important role in the antiestrogenic activity of DEPs. In particular, F4, which contains PAH and its derivatives, showed the highest antiestrogenic activity. Since in our previous study, dibenzo(a, h)anthracene and chrysene were identified in F4, and these chemicals have antiestrogenic activity, we assume that these chemicals are the major causative chemicals with antiestrogenic activity in DEPs. In contrast to the estrogenic activity of DEPs, antiestrogenic activity of CE was stronger than that of antiestrogenic fractions (F3 and F4) at non-cytotoxic concentrations, indicating that additive or synergistic effects by unidentified chemicals contained in DEPs occurred

참고문헌 (Reference)

1 Gill, L., "Trends of polycyclic aromatic hydrocarbon levels and mutagenicity in Santiago’s inhalable airborne particles in the period, 1992-1996" 12 : 1185-1204, 2000

2 Perez, P., "The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the central carbon and the hydroxyl group" 106 : 167-174, 1998

3 Tran, D. Q., "The anti-estrogenic activity of selected polynuclear aromatic hydrocarbons in yeast expressing human estrogen receptor" 229 : 102-108, 1996

4 Oenga, G. N., "TCDD and PCBs inhibit breast cancer cell proliferation in vitro" 18 : 811-819, 2004

5 Hanberg, A., "Swedish dioxin survey: induction" 69 : 442-449, 1991

6 Kwon, S. B., "Size-dependent volatility of diesel nanoparticles: Chassis dynamometer experiments" 37 : 1794-1802, 2003

7 Chaloupka, K., "Polynuclear aromatic hydrocarbon carcinogens as antiestrogens in MCF-7 human breast cancer cells: Role of the Ah receptor" 13 : 2233-2239, 1992

8 Safe, S., "Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds" 67 : 247-281, 1995

9 Vondráèek, J., "Modulation of estrogen receptor-dependent reporter construct activation and G0/G1-S-phase transition by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells" 70 : 193-201, 2002

10 Hashimoto, Y., "Measurement of estrogenic activity of chemicals for the development of new dental polymers" 15 : 421-425, 2001

11 Higgins, K. J., "Kinetics of diesel nanoparticle oxidation" 37 : 179-190, 2003

12 Safe, S., "Interactions between hormone and chemicals in breast cancer" 38 : 121-158, 1998

13 Fertuck, K. C., "Interaction of PAH-related compounds with the a and b isoforms of the estrogen receptor" 121 : 167-177, 2001

14 Safe, S., "Inhibitory aryl hydrocarbon receptorestrogen receptor alpha cross-talk and mechanisms of action" 16 : 807-816, 2003

15 Watanabe, N., "Inhalation of diesel engine exhaust affects spermatogenesis in growing male rats" 107 : 539-544, 1999

16 Li, C., "Impairment of testicular function in adult male Japanese quail (Coturnix japonica) after a single administration of 3-methyl-4-nitrophenol in diesel exhaust particles" 189 : 555-564, 2006

17 Noguchi, K., "Identification of estroenic/anti-estrogenic compounds in diesel exhaust particulate extract" 21 : 1135-1142, 2007

18 U.S.Environmental Protection Agency(EPA), "Health assessment document for diesel engine exhaust, Prepared by the National Center for Environmental Assessment, Washington, DC, for the Office of Transportation and Air Quality; EPA/600/8-90/057F"

19 Yoshida, S., "Exposure to diesel exhaust affects the male reproductive system of mice" 22 : 307-315, 1999

20 Olea, N., "Estrogenicity of resin-based composities and sealants used in dentistry" 104 : 298-305, 1996

21 Taneda, S., "Estrogenic and anti-estrogenic activity of nitrophenols in diesel exhaust particles (DEP)" 27 : 835-837, 2004

22 Taneda, S., "Estrogenic and anti-estrogenic activities of two types of diesel exhaust particles" 170 : 153-161, 2002

23 Furuta, C., "Estrogenic activities of nitrophenols in diesel exhaust particles" 70 : 1527-1533, 200

24 Mori, Y., "Estrogenic activities of chemicals in diesel exhaust particles" 25 : 145-146, 2002

25 Martin, M. B., "Estrogen-like activity of metals in MCF-7 breast cancer cells" 144 : 2425-2436, 2003

26 Clunies-Ross, C., "Dioxins in diesel exhaust" 381 : 379-, 1996

27 Gozgit, J. M., "Differential action of polycyclic aromatic hydrocarbons on endogenous estrogen-responsive genes and on a transfected estrogen-responsive reporter in MCF-7 cells" 196 : 58-67, 2004

28 Safe, S., "Dietary and environmental estrogens and antiestrogens and their possible role in human disease" 1 : 29-33, 1994

29 Tsukue, N., "Diesel exhaust affects the abnormal delivery in pregnant mice and the growth of their young" 14 : 635-651, 2002

30 Tsukue, N., "Diesel exhaust (DE) affects the regulation of testicular function in male Fishcher 344 rats" A 63 : 115-126, 2001

31 Plíšková, M., "Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events" 83 : 246-256, 2005

32 Topinka, J., "DNA adduct formation in mammalian cell cultures by polycyclic aromatic hydrocarbons (PAH) and nitro-PAH in coke oven emission extract" 419 : 91-105, 1998

33 Bayona, J. M., "Characterization of polar polycyclic aromatic compounds in a heavy-duty diesel exhaust particulate by capillary column gas chromatography and high-resolution mass spectrometry" 22 : 1440-1447, 1988

34 Lewtas, J., "Bioassaydirected fractionation of the organic extract of SRM1649 urban air particulate matter" 39 : 245-256, 1990

35 Schuetzle, D., "Bioassay-directed chemical analysis in environmental research" 58 : 1060A-1075A, 1986

36 Machala, M., "Aryl hydrocarbon receptor–mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments" 20 : 2736-2743, 2001

37 Wang, W. L., "Aryl hydrocarbon receptormediated antiestrogenicity in MCF-7 cells: Modulation of hormone-induced cell cycle enzymes" 356 : 239-248, 1998

38 Arcaro, K. F., "Antiestrogenicity of environmental polycyclic aromatic hydrocarbons in human breast cancer cells" 133 : 155-127, 1999

39 Buchanan, D. L., "Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse uterus: critical role of the aryl hydrocarbon receptor in stromal tissue" 57 : 302-311, 2000

40 Navas, J. M., "Antiestrogenic activity of anthropogenic and natural chemicals" 5 : 75-82, 1998

41 Meek, M. D., "Ah receptor and estrogen receptor-dependent modulation of gene expression by extracts of diesel exhaust particles" 79 : 114-121, 1998

42 Charles, G. D., "Activity of benzo(a)pyrene and its hydroxylated metabolites in an estrogen receptor-a reporter gene assay" 55 : 320-326, 2000

43 Safe, S., "2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) and related compounds as antioestrogens: characterization and mechanisms of action" 69 : 400-409, 1991