本研究目的在於探討萘醌之鄰位醌類代謝物（ortho-quinonoid）經由氧化還原循環生成活性氧化物（reactive oxygen species, ROS）之潛力，進而對核酸產生氧化破壞作用，包括去鹼基核酸（AP sites）及DNA單股斷鏈（DNA SSB）之作用機制。研究結果顯示，萘之鄰位醌類活性代謝物，包括1,2-naphthoquinone (1,2-NQ)及1,2-dihydroxynaphthalene (1,2-NCAT)，於活體外與小牛胸腺DNA（ctDNA）反應，皆可在過渡性金屬Cu(II)（20 μM）及NADPH（100 μM）的存在下，誘發ctDNA之DNA SSB及AP sites同步生成。經由添加ROS移除劑及抗氧化劑之結果顯示，1,2-NQ在Cu(II)及NADPH存在下，可經由氧化還原循環生成ROS而誘發AP site之核酸損害作用，其主要之ROS物種為H2O2，•OH則可能提供部分作用。由於Cu(I)-specific螯合劑能抑制Cu(II)與1,2-NQ誘發的AP sites之生成，此一結果顯示Cu(II)/Cu(I)間的氧化還原循環作用在此反應扮演重要角色，同時Cu(I)與ROS中之H2O2所結合之過氧化物－Cu(I)OOH，可能為實際參與誘發DNA SSB及AP sites生成之物種。此外，生物體內小分子物質glutathione (GSH)，可抑制Cu(II)與1,2-NQ所誘發的AP sites之生成，顯示GSH可能是與1,2-NQ結合後中斷其氧化還原之循環，終止ROS生成進而抑制DNA之氧化損壞作用。此外，GSH亦有可能是直接與ROS反應，移除ROS達到保護DNA之作用。相對於ROS所誘發之AP sites，1,2-NQ則需高濃度（5 mM）時與核酸形成DNA adduct，再進行去嘌呤作用才能生成AP sites。此外，1,2-NQ經由氧化還原循環產生ROS而誘發之AP sites種類，經確認約70%為putrescine可切除之AP sites。總結本研究之結果證實，萘之鄰位醌類代謝物可經由誘發ROS進而導致核酸之五碳醣之氫原子移除作用（hydrogen abstraction），造成同步生成DNA SSB及AP sites之核酸損壞。

Oxidative DNA damage induced by quinoid metabolites of naphthalene, e.g., 1,2-naphthoquinone (1,2-NQ), 1,2-dihydroxynaphthalene (1,2-NCAT), was investigated in calf thymus DNA (ctDNA). Results indicated that in the presence of Cu(II) and NADPH, parallel increases in DNA strand breaks and abasic (AP) sites was detected in calf thymus DNA exposed to 1,2-NQ and 1,2-NCAT over the corresponding control. Further investigation indicated that the DNA damage induced by 1,2-NQ plus Cu(II) and NADPH was inhibited by the additions of catalase, copper(I)-specific chelator, hydroxyl radical scavenger and glutathione whereas superoxide dismutase did not prevent the induction of AP sites. These results suggest the involvement of Cu(I)、hydrogen peroxide and hydroxyl radical in the induction of oxidative DNA damage by 1,2-NQ. At high concentration ( 5 mM ), naphthalene quinoid alone may induce AP sites via epurination/ depyrimidination naphthalene quinone-DNA adducts. In contrast, of induced AP sites in.Further characterization of the AP sites confirmed that 1,2-NQ induced predominantly（70％）putrescine-excisable AP sites in ctDNA. In summary, quinononid derivatives of naphthalene may induce significant oxidative modifications in ctDNA via hydrogen abstract atome from deoxyribose, resulting in the parallel formation of AP sites and strand breaks.

中 文 摘 要 I
Abstract III
縮 寫 表 IV
目 錄 ……………………………………………………………………………………. V
圖 目 錄 VII
第一章 前 言 1
1-1 研究緣起 1
1-2 研究目的 1
第二章 文獻回顧 3
2-1 多環芳香族碳氫化合物（PAHs） 3
2-1-1 PAHs之簡介 3
2-1-2 PAHs醌類化物之致基因毒害作用與活性氧化物（ROS）之生成 3
2-2 萘之代謝途徑及致基因毒害作用 6
2-2-1萘（naphthalene）之物化特性及健康危害 6
2-2-2萘之代謝途徑 7
2-2-3萘醌類化合物之致基因毒害作用 9
2-3 氧化所引起之DNA損害作用（oxidative DNA damage） 10
2-3-1 活性氧化物（reactive oxygen species, ROS） 10
2-3-2 氧化壓力誘發之DNA損害（DNA damage resulting from oxidative stress） 11
2-3-3 生物體之抗氧化防禦系統 12
2-3-4 氧化壓力與疾病之相關性 13
2-4 DNA損害修補 14
2-4-1 DNA損害之修補機制 14
2-4-2去鹼基核酸 18
2-5去鹼基核酸之偵測 19
第三章 實驗材料與方法 23
3-1 實驗材料 23
3-1-1 水 23
3-1-2 化學藥品 23
3-1-3 去鹼基核酸分析藥品 23
3-1-4 電泳分析藥品 24
3-1-5 實驗設備 24
3-2 實驗方法 24
3-2-1 鄰位萘醌誘發DNA氧化損壞作用之能力 24
3-2-2 萘醌誘發DNA氧化損壞作用之機制 25
3-2-3 萘醌誘發核酸生成3’-及5’-cleaved AP sites之結構確認 27
3-3分析方法 27
3-4 數據分析 32
第四章 實驗結果 33
4-1萘醌誘發DNA氧化損害作用之能力 33
4-1-1 1,2-萘醌（1,2-NQ）誘發DNA AP sites與DNA SSB之生成 33
4-1-2過渡性金屬離子與NADPH之影響 36
4-1-3 1,2-dihydroxynaphthalene（1,2-NCAT）誘發DNA AP sites之生成 38
4-1-4 NADPH及銅之存在對1,2-NQ及1,2-NCAT誘發DNA AP sites之影響 39
4-2萘醌誘發DNA氧化損壞作用之機制 41
4-2-1 ROS移除劑之影響 41
4-2-2抗氧化劑之影響 44
4-2-3 Cu(I) 螯合劑（bathocuproinedisulfonic acid, BAT）之影響 44
4-2-4 還原態麩胱甘胺（glutathione, GSH）及cysteine之影響 46
4-3萘醌誘發DNA生成3’ 端或5’ 端斷裂之AP sites （3’-及5’-cleaved AP sites）之結構確認 49
第五章 討 論 51
第六章 結論與建議 56
6-1 結論 56
6-2未來研究方向及建議 57
參考文獻 59

陳嘉芬。1999。現代遺傳學。藝軒圖書出版社。pp. 433-461
Anderson, D. (1996) Antioxidant defences against reactive oxygen species causing geneticc and other damage. Mutat. Res., 350, 103-108.
Anon (1992) Toxicology and carcinogenesis studies of naphthalene (Cas No. 91-20-3) in B6C3F1 mice (inhalation studies). National Toxicology Program Technical Report series, No. 410.
Bagchi, M., Bagchi, D, Balmoori, J., Ye, X. and Stohs, S.J. (1998) Naphthalene induced oxidative stress and DNA damage in cultured macrophage J774A.1 cells. Free Radical Biol. Med., 25, 137-143.
Bakeeva, L.E., Zamyatnina, V.A., Shorning, B.Y., Aleksandrushkina, N.I. and Vanyushin, B.F. (2002) Effect of the antioxidant ionol (BHT) on growth and development of etiolated wheat seedlings: control of apoptosis, cell division, organelle ultrastructure, and plastid differentiation. Biochemistry, (Mosc) 66, 850-859.
Beckman, K.B. and Ames, B.N. (1998) The free radical theory of aging matures. Physiol. Res., 78, 547-581.
Belett B. S., Stadtman, E. R. (1997) Protein oxidative aging, disease, and oxidative stress. J. Biol. Chem., 272, 20313-20316.
Bock, K.W., Van Ackeren, G., Lorch, F. and Birke, F.W. (1976) Metabolism of naphthalene to naphthalene dihydrodiol glucronide in isolated hepatocytes and in liver microsomes. Bioshem. Pharmacol., 25, 2351-2356.
Braithwaite, E., Wu, X. and Wang, Z. (1999) Repair of DNA lesions: mechanisms and relative repair efficiencies. Mutation Research, 424(1-2), 207-219.
Breen, A.P. and Murphy, J.A. (1995) Reactions of oxyl radicals with DNA. Free Radical. Biol. Med., 18, 1033-1077.
Buckpitt A, Chang AM, Weir A, Van Winkle L, Duan X, Philpot R, Plopper C. (1995) Relationship of cytochrome P450 activity to Clara cell cytotoxicity. IV. Metabolism of naphthalene and naphthalene oxide in microdissected airways from mice, rats, and hamsters. Mol. Pharmacol, 47, 74-81.
Buffinton, G.D., Öllinger, K., Brunmark, A. and Cadenas, E. (1989) DT- diaphorase- catalysed reduction of 1,4 naphthoquinone derivatives and glutathionyl-quinone conjugates. Bioch. J., 257, 561-571
Buonarati, M., Morin, D., Plopper, C. and Buckpitt, A. (1989) Glutathione depletion and cytotoxicity by naphthalene 1,2 oxide in isolated hepatocytes. Chem-Biol. Interact., 71,147-165.
Butterworth, M., Lau, S. S., and Monks, T. J. (1998) 2-Hydroxy-4-glutathion-S-yl-17 beta- estradiol and 2-hydroxy-1-glutathion-S-yl-17 beta- estradiol produce oxidative stress and renal toxicity in an animal model of 17beta-estradiol-mediated nephrocarcinogenicity. Carcinogenesis, 19, 133-139.
Cadenas, E. and Davies K.J. (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radical Biol.Med., 29, 222-230.
Chen, Y., Shen, L., Zhang, F., Lau, S. S., van Breemen, R. B., Nikolic, D. and Bolton, J. L. (1998) The equine estrogen metabolite, 4-hydroxyequilenin causes DNA single-strand breaks and oxidation of DNA bases in vitro. Chem. Res. Toxicol., 11, 1105-1111.
Cheng, K.C., Cahill, D.S., Kasai, H., Nishimura, S. and Loeb, L.A. (1992) 8- hydroxyguanine, a abundant form of oxidative DNA damage, causes GT and AC substitution. J. Biol. Chem., 267, 166-172.
Chisolm, G.M. and Steinberg, D. (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic. Biol. Med., 28, 1815-1826.
Cho, M., Jedrychowski, R., Hammock, B. and Buckpitt, A. (1994) Reactive naphthalene metabolite binding to hemoglobin and albumin. Fund. Appl. Toxicol., 22, 26-33.
Crittenden, B.D.and Long, R. (1976) Polycyclic Aromatic Hydrocarbon: Chemistry, Metabolism and Carcinogesis. Freudeuthal, R.I., Jones, P.Eds. Ranven Press. New York.
Dean, R.T., Fu, S., Stocker, R. and Davier, M.J. (1997) Biochemistry and pathology of radical-mediated protein oxidation. Biochem. J., 324, 1-8.
Degawa, M., Arai, H., Miura, S. and Hashimoto, Y. (1993) Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat. Carcinogenesis, 14,1091-1094.
Dizdaroglu, M. (1992) Oxidative damage to DNA in mammalian chromatin. Mutat. Res., 275, 331-342.
Drouin, R., Rodriguez, H., Gao, S. A., Gebreyes, Z., O’Connor, T. R., Holmquist, G. P., and Akman, S. A. (1996) Cupric ion/ascorbate/hydrogen peroxide-induced DNA damage: DNA-bound copper ion primarily induces base modifications. Free Radical Biol. Med., 21, 261-273.
Faverney, C. Risso-de, Lafaurie, M., Girard, J. P. and Rahmani, R. (2000) The nitroxide stable radical tempo prevents metal-induced inhibition of CYP1A1 expression and induction. Toxicology Latters, 111, 219-227.
Flowers, L., Ohnishi, S.T. and Penning, T.M. (1997) DNA strand scission by polycyclic aromatic hydrocarbon o-quinones: role of reactive oxygen species, Cu(II)/Cu(I) redox cycling, and o-semiquinone anion radicals. Biochemistry, 36, 8640-8648.
Fridovich I. (1997) Superoxide anion redaical superoxide dismutases, and related matters. J. Biol. Chem., 272:18515-18517.
Friedberg, E.C., Walker, G.C. and Siede, W. (1995) DNA repair and mutagenesis. American Society of Microbiology press, Washington (D.C.).
Froystein, N.A., Davis, J.T., Reid, B.R. and Sletten, E. (1993) Sequence-selsctive metal ion binding to DNA oligonucleotide. Acta. Chem. Scand., 47,649-657.
Germansky, M and Jamall, I.S. (1988) Organ-specific effects of naphthalene on tissue peroxidation, glutathione peroxidases and superoxide dismutase in the rat. Arch. Toxicol., 61, 480-483.
Ghetti, G. and Mariani, L. (1956) Eye changes due to naphthalene. Med. Lav., 47, 524.
Halliwell, B. and Gutteridge, J.M. (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J., 219, 1-14
Hatherill, R., Till, G..O., Ward, P.A. (1991) Mechanisms of oxidant-induced changes in erythrocytes. Agents Actions, 32, 351-357.
Hensley, K., Robinson, K.A., Gabbita, S.P., Salsman, S. and Floyd, R.A. (2000) Reactive oxygen species, cell signaling, and cell injury. Free Radical Biol. Med., 28, 1456-1462.
Hirakawa, K., Oikawa, S., Hiraku, Y., Hirosawa, I. and Kawanishi, S. (2002) Catechol and hydroquinone have different redox properties responsible for their differential DNA-damaging ability. Chem. Res. Toxicol., 15,76-82.
Höke, H. and Zellerhoff, R. (1998) Metabolism and toxicity of diisopropylnaphthalene as compared to naphthalene and monoalkyl naphthalenes: a minireview. Toxicology, 126, 1-7.
Jones, G..D. and Weinfeld, M. (1996) Dual action of tirapazamine in the induction of DNA strand breaks. Cancer Res., 56, 1584-1590.
Kasai, H. (1997) Analysis of a form of oxidative DNA damage, 8-hydroxy-2’- deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutat. Res., 387, 147-163.
Kawanishi, S., Hiraku, Y. and Oikawa, S. (2001) Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging. Mutat. Res., 488, 65-76.
Krishna, M.C., Samuni, A., Taira, J., Goldstein, S., Mitchell, J.B. and Russo, A. (1996) Stimulation by nitroxides of catalase-like activity of hemeproteins. Kinetics and mechanism. J. Biol. Chem., 271, 26018—26025
Kubo, K., Ide, H., Wallace, S.S. and Kow, Y.W. (1992). A novel, sensitive, and specific assay for abasic sites, the most commonly produced DNA lesion. Biochemistry, 31, 3703-3708.
Kulisch, G.P. and Vilker, V.L. (1991) Application of Pseudomonas pulid PpG786 containing P-450 cytochrome monooxygenase for removal of trace naphthalene concentrations. Biotechnol. Prog., 7, 93-98.
Lauriault, V.V., Khan, S. and O''Brien, P.J. (1992) Hepatocyte cytotoxicity induced by various hepatotoxins mediated by cytochrome P-450IIE1: protection with diethyldithiocarbamate administration. Chem.-Biol. Interact., 81, 271-289
Lehninger, A.L., Nelson, D.L. and Cox, M.M. (1993) Principle of biochemistry. Worth Publisher, Inc. New York.
Li, Y. and Trush, M.A. (1994) Reactive oxygen-dependent DNA damage resulting from the oxidation of phenolic compoundsby a copper-redox cycle mechanism. Cancer Res., 54, 1895-1898.
Li, Y., Trush, M. A., and Yager, J. D. (1994) DNA damage caused by reactive oxygen species originating from a copper-dependent oxidation of the 2-hydroxy catechol of estradiol. Carcinogenesis, 15, 1421-1427.
Lin, P.H., Nakamura,J., Yamaguchi, S., La, D.K. and Swenberg, J.A. (2001a) Oxidative damage and direct adducts in calf thymas DNA induced by tetrachlorohydroquinone and tetrachloro-1,4-benzoquinone. Carcinogenesis, 22, 627-634.
Lin, P.H., Nakamura, J., Yamaghuji, Y., and Swenberg, J.A. (2001c) Reactive oxygen-mediated induction of 5’-cleaved apurinic/apyrimidinic sites in calf thymus DNA by quinonoid metabolites of 17b-estradiol. Presented at the 40th annual meeting of the Society of Toxicology held in San Francisco, CA, USA.
Lin, P.H., Nakamura, J., Yamaguchi, S., La, D.K., Upton, P.B. and Swenberg, J.A. (2001b) Induction of direct adducts, 5’-cleaved apurinic/apyrimidinic sites, and oxidized bases in nuclear DNA of human HeLa S3 tumor cells by tetrachlorohydroquinone. Carcinogenesis, 22, 635-639.
Lindahl, T. and Nyberg, B. (1972) Rate of depurination of native deoxyribonucleic acid. Biochemistry, 11, 3610—3618.
Linder, M.C. (1991) Nautritional Biochemistry and Metabolism. New York: Elsevier Science.
Liu, C., Zhou, J., Li, O., Wang, L., Liao, Z., and Xu, H. (1999) DNA damage by copper(II) complexs: coordination-structural dependence of reactivities. J. Inorganic Biochemistry., 75, 233-240.
Lubek, B.M., Kubow, S., Basu, P.K. and Wells, P.G.. (1989) Cataractogenicity and bioactivation of naphthalene derivatives in lens culture and in vivo. Lens Eye Toxic. Res. 6, 203-209.
Martínez-Cayuela M. (1995) Oxygen free radicals and human disease. Biochimie., 77, 147-161.
McCoull, K.D., Rindgen, D., Blai,r I.A. and Penning, T.M. (1999) Synthesis and characterization of polycyclic aromatic hydrocarbon o-quinone depurinating N7-guanine adducts. Chem Res Toxicol., 12, 237-246.
Milne, L., Nicotera, P., Orrenius, S. and Burkitt, M.J. (1993) Effects of glutathione and chelating agents on copper-mediated DNA oxidation: Pro-oxidant and antioxidant properties of glutathione. Arch. Biochem. Biophys,. 304, 102-109.
Mitchell, J.B., Samuni, A., Krishna, M.C., DeGraff, W.G., Ahn, M.S., Samuni, U. and Russo, A. (1990) Biologically active metal-independent superoxide dismutase mimics. Biochemistry, 29, 2802—2807
Murty, V.S. and Penning, T.M. (1992) Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1,2-dione. Chem. Biol. Interact., 84, 169-188.
Naito, S., Ono, Y., Somiya, I., Inoue, S., Ito, K., Yamamoto, K. and Kawanishi, S. (1994) Role of active oxygen species in DNA damage by pentachlorophenol metabolites. Mutat. Res., 310, 79-88.
Nakamura, J. and Swenberg, J.A. (1999) Endogenous apurinic/aptrimidinic sites in genomic DNA mammalian tissues. Cancer Res., 59, 2522—2526
Nakamura, J., Walker, V.E., Upton, P.B., Chiang, S.Y., Kow, Y.W. and Swenberg, J.A. (1998) Highly sensitive apurinic/apyrimidinic sites assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res., 58, 222-225.
Neto, J.B., Gentil, A., Cabral, R.E. and Sarasin, A. (1992) Mutation spectrum of heat-induced abasic sites on a single-stranded shuttle vector replicated in mammalian cells. J. Biol. Chem., 267, 19718-19723.
Oikawa, S. and Kawanishi, S. (1998) Distinct mechanisms of site-specific DNA damage induced by endogenous reductants in the presence of iron(III) and copper(II). Biochim Biophys Acta., 1, 19-30
Öllinger, K. and Brunmark, A. (1991) Effect of hydroxy substituent position on 1,4-naphthalenequinone toxicity to rat hepatocytes. J. Biol. Chem., 266, 21496-21503.
Parry, J.M. (1992) Prediction of the carcinogenic potential of chemicals. Mutagenesis, 7, 1-2
Penning, T.M., Ohnishi, S.T., Ohnishi, T. and Harvey, R.G.. (1996) Generation of reactive oxygen species during the enzymatic oxidation of polycyclic aromatic hydrocarbon trans-dihydrodiols catalyzed by dihydrodiol dehydrogenase. Chem Res Toxicol., 9, 84-92
Puga, A., Maier, A. and Medvedovic, M. (2000) The Transcriptional Signature of Dioxin in Human Hepatoma Hepatoma HepG2. Cells. Biol. Pharmacol,. 60,1129-1142.
Ramana, C.V., Boldogh, I., Izumi, T. and Mitra, S. (1998) Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals. Proc. Natl. Academ. Sci., 95, 5061-5066.
Richter, C., Park, J.W., and Ames, B.N. (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci., 85, 6465-7467.
Rosenquist, T.A., Zharkov, D.O. and Grollman, A.P. (1997) Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase. Proc. Natl. Acad. Sci., U S A 94,7429-7434.
Russell, P., Yamada, T., Xu, G.T., Garland, D.and Zigler, J.S. Jr. (1991) Effects of naphthalene metabolites on cultured cells from eye lens. Free Rad. Biol. Med., 10, 255-261
Samuni, A., Krishna, C.M., Riesz, P., Finkelstein, E., and Russo, A. (1988) A novel metal-free low molecular weight superoxide dismutase mimic. J. Biol. Chem., 263, 17921—17924
Schaeffer, V., Mpanza, Z. and Thakker, D. (1987) Novel stereoselectivity of rat liver cytochromes P450 in the metabolism of (1S,2S)-dihydrodiols and (1R,2R)-dihydrodiols of naphthalene to diol epoxides. Fed. Proc., 46, 865.
Schweigert, N., Acero, J.L., Gunten, U.V., Canonica, S., Zehnder, A.J.B. and Eggen, R. I. L. (2000) DNA degration by mixture of copper and catechol is caused by DNA-copper-hydroperoxo complexes, probably DNA-Cu(I)OOH. Environmental and Molecular Mutagenesis., 36, 5-12.
Seaton, T.A., Cooper, J.M., and Schapira, A.H.V. (1997) Free radical scavengers protect dopaminergic cell lines from apoptosis induced by complex I inhibitors. Brain Research, 777, 110-118.
Shigenaga, M. K., and Ames, B. N. (1991) Assays for 8-hydroxy-2’-deoxyguanosine : A biomarker of in vivo oxidative DNA damage. Free Radical Biol. Med., 10, 211-216.
Shultz, M.A., Choudary, P.V. and Buckpitt, A.R. (1999) Role of murine cytochrome P-450 2F2 in metabolic activation of naphthalene and metabolism of other xenobiotics. J. Pharmacol Exp. Ther., 290, 281-288.
Smith, M.T. and Evans, C.G. (1984) Inhibitory effect of superoxide-generating quinones on superoxide dismutase. Biochem. Pharmacol., 33, 3109-3110.
Smithgall, T.E., Harvey, R.G. and Penning, T.M. (1986) Regio- and stereospecificity of homogeneous 3 alpha-hydroxysteroid-dihydrodiol dehydrogenase for trans-dihydrodiol metabolites of polycyclic aromatic hydrocarbons. J. Biol. Chem., 261, 6184-6191.
Smithgall, T.E., Harvey, R.G. and Penning, T.M. (1988) Spectroscopic identification of ortho-quinones as the products of polycyclic aromatic trans-dihydrodiol oxidation catalyzed by dihydrodiol dehydrogenase. A potential route of proximate carcinogen metabolism. J. Biol. Chem., 263, 1814-1820.
Talpaert-Borle, M. and Liuzzi, M. (1983) Reaction of apurinic/apyrimidinic sites with [14C]methoxyamine. A method for the quantitative assay of AP sites in DNA. Biochim. Biophys Acta,. 740, 410-416.
Telang, N.T., Katdara, M., Bradlow, H.L., and Osborne, M. (1997) Estrodiol metabolism: an endocrine biomarker for modulation of human mammary carcinogenesis. Environ. Health Perspect., 105, (suppl 3) 559-564.
Thibodeau, P.A., Kocsis-Bedard, S., Courteau, J., Niyonsenga, T., Paquette, B. (2001) Thiols can either enhance or suppress DNA damage induction by catecholestrogens. Free Radic Biol Med., 30, 62-73.
Tingle, M.D., Pirmohamed, M., Templeton, E., Wilson, A.S., Madden, S., Kitteringham, N. R. and Park, B.K. (1993) An investigation of the formation of cytotoxic, genotoxic, protein-reactive and stable metabolites from naphthalene by human liver microsomes. Biochem. Pharmacol,. 46, 1529-1538.
Tsutsui, T., Suzuki, N., Fukuda, S., Sato, M., Maizumi, H., McLachlan, J.A. and Barrett, J.C. (1987) 17b-estrodiol-induced cell transformation and aneuploidy of Syrian hamster embryo cells in culture. Carcinogenesis, 8, 1715-1719.
Verhaegh, G.H., Richard, M.J. and Hainaut, P. (1997) Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulations p53 DNA-binding activity by increasing the intracellular level of copper. Mol. Cell. Biol., 17, 5699-5706.
Vuchetich, P.J., Bagchi, D, Bagchi, M., Hassoun, E.A., Tang, L., Stohs, S.J. (1996) Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate. Free Radical Biol. Med., 21, 577-590.
Weinfeld, M. and Soderlind, K.J. (1991) 32P-postlabeling detection of radiation-induced DNA damage: identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry, 30, 1091-1097.
Weinfeld, M., Liuzzi, M. and Paterson, M.C. (1990) Response of phage T4 polynucleotide kinase toward dinucleotides containing apurinic sites: design of a 32P-postlabeling assay for apurinic sites in DNA. Biochemistry, 29, 1737-1743.
Wilson, A.S., Davis, C.D., Williams, D.P., Buckpitt, A.R., Pirmohamed, M. and Park, B.K. (1996) Characterisation of the toxic metabolite(s) of naphthalene. Toxicology, 114, 233-242
Wilson, A.S., Tingle, M.D., Kelly, M.D. and Park, B.K. (1995) Evaluation of the generation of genotoxic and cytotoxic metabolites of benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen using human liver microsomes and human lymphocytes. Hum. Exp. Toxicol., 14, 507-515.
Wolf, O. (1976) Cancer among chemical workers of a naphthalene cleaning plant. Dtsch. Gesund. Heitsw., 31, 996-999.
Wolf, O. (1978) Carcinoma of the larynx in naphthalene workers. Z. Gesamte Hyg., 24, 737-739.
Yakes, F. M., and Van Hiuten, B. (1997) Mitochobdrial DNA damage is more extensive and persists longer that nuclear DNA damage in human cells following oxidative stress. Proc. Natl Acad Sci, USA 94, 514-519.
Yamauchi, T., Komura, S. and Yagi, K. (1986) Serum lipid peroxide levels of albino rats administered naphthalene. Biochem. Int., 13, 1-6.