Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen δ-aminolevulinic acid
Małgorzata Karbownik
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Department of Thyroidology, Institute of Endocrinology, Medical University of Łódź, Łódź, Poland
Search for more papers by this authorDun-xian Tan
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Search for more papers by this authorCorresponding Author
Russel J. Reiter
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center, Mail Code 7762, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. Fax: 210-567-6948Search for more papers by this authorMałgorzata Karbownik
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Department of Thyroidology, Institute of Endocrinology, Medical University of Łódź, Łódź, Poland
Search for more papers by this authorDun-xian Tan
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Search for more papers by this authorCorresponding Author
Russel J. Reiter
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA
Department of Cellular and Structural Biology, University of Texas Health Science Center, Mail Code 7762, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. Fax: 210-567-6948Search for more papers by this authorAbstract
Well known are the anti-oxidant, free radical–scavenging and anti-tumorigenic properties of melatonin. δ-Aminolevulinic acid (ALA) is a precursor of heme synthesis. When over-produced and accumulated in tissues, ALA is a potential carcinogen, such as in the course of acute intermittent porphyria, hereditary tyrosinemia and lead poisoning. Our aim was to examine the potential protective effect of melatonin against oxidative damage to nuclear DNA and membrane lipids in rat lung and spleen caused by ALA. Changes in 8-hydroxy-2`-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and the level of malondialdehyde + 4-hydroxyalkenals, an index of lipid peroxidation, were measured. Rats were injected with ALA (i.p., 40 mg/kg body weight, every other day) and/or with melatonin (i.p., 10 mg/kg body weight, 3 times daily) for 2 weeks. Both 8-OHdG and lipid peroxidation levels increased significantly in lung and spleen due to ALA treatment. Co-treatment with melatonin completely counteracted the effects of ALA. In conclusion, melatonin effectively protects nuclear DNA and lipids in rat lung and spleen against oxidative damage caused by the carcinogen ALA, and the indole may be of value as a supplement in patients suffering from molecular damage related to ALA accumulation. Int. J. Cancer 88:7–11, 2000. © 2000 Wiley-Liss, Inc.
REFERENCES
- Antolin,I., Rodriguez,C., Sainz,R.M., Mayo,J.C., Uria,H., Kotler,M.L., Rodriguez-Colunga,M.J., Tolivia,D. and Menendez-Pelaez,A., Neurohormone melatonin prevents cell damage: effect on gene expression for anti-oxidant enzymes. FASEB J., 10, 882-890 (1996).
- Antunes,F., Barclay,L.R.C., Ingold,K.U., King,M., Norris,J.Q., Scaiano,J.C. and Xi F., On the anti-oxidant activity of melatonin. Free Radic. Biol. Med., 26, 117-128 (1999).
- Benot,S., Goberna,R., Reiter,R.J., Garcia-Maurino,S., Osuna,C. and Guerrero,J.M., Physiological levels of melatonin contribute to the anti-oxidant capacity of human serum. J. Pineal Res., 27, 59-64 (1999).
- Bjersing,L., Andersson,C. and Lithner,F., Hepatocellular carcinoma in patients from northern Sweden with acute intermittent porphyria: morphology and mutations. Cancer Epidemiol. Biomarkers Prevent., 5, 393-397 (1996).
- Blask,D.E., Melatonin in oncology. In: H.S. Yu and R.J. Reiter (eds.), Melatonin: biosynthesis, physiological effects, and clinical applications, pp. 447-475, CRC Press Boca Raton FL 1993).
- Bradford,M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254 (1976).
- Burcham,P.C., Genotoxic lipid peroxidation products: their DNA damaging properties and role in formation of endogenous DNA adducts. Mutagenesis, 13, 287-305 (1998).
- Carneiro,R.C.G. and Reiter,R.J., δ-Aminolevulinic acid-induced lipid peroxidation in rat kidney and liver is attenuated by melatonin: an in vitro and in vivo study. J. Pineal Res., 24, 131-136 (1998).
- Casas,A., Fukuda,H. and Battle,A.M.C., Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles. Brit. J. Cancer, 81, 13-18 (1999).
- De Zwart,L.L., Meerman,J.H.N., Commandeur,J.N.M. and Vermeulen,N.P.E., Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic. Biol. Med., 26, 202-226 (1999).
- Di Mascio,P., Teixeira,P.C., Onuki,J., Medeiros,M.H.G., Dörnemann, D., Douki,T. and Cadet,J., DNA damage by 5-aminolevulinic and 4,5-dioxovaleric acids in the presence of ferritin. Arch. Biochem. Biophys., 373, 368-374 (2000).
- Douki,T., Onuki,J., Medeiros,M.H.G., Bechara,E.J.H., Cadet,J. and Di Mascio,P., Hydroxyl radicals are involved in the oxidation of isolated and cellular DNA bases by 5-aminolevulinic acid. FEBS Lett., 428, 93-96 (1998).
- Fraga,C.G., Onuki,J., Lucesoli,F., Bechara,E.J.H. and Di Mascio,P., 5-Aminolevulinic acid mediates the in vivo and in vitro formation of 8-hydroxy-2`-deoxyguanosine in DNA. Carcinogenesis, 15, 2241-2244 (1994).
-
Hillemanns,P.,
Korell,M.,
Schmitt-Sody,M.,
Baumgartner,R.,
Beyer,W.,
Kimmig,R.,
Untch,M. and
Hepp,H.,
Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid.
Int. J. Cancer,
81,
34-38
(1999).
10.1002/(SICI)1097-0215(19990331)81:1<34::AID-IJC7>3.0.CO;2-H CAS PubMed Web of Science® Google Scholar
- Linet,M.S., Gridley,G., Nyrén, O., Mellemkjaer,L., Olsen,J.H., Keehn,S., Adami,H.O. and Fraumeni,J.F., Primary liver cancer, other malignancies, and mortality risks following porphyria: a cohort study in Denmark and Sweden. Amer. J. Epidemiol., 149, 1010-1015 (1999).
- McGillion,F.B., Thompson,G.G. and Goldberg,A., Tissue uptake of δ-aminolevulinic acid. Biochem. Pharmacol., 24, 299-301 (1975).
- Menendez-Pelaez,A. and Reiter,R.J., Distribution of melatonin in mammalian tissues: the relative importance of cytosolic versus nuclear localization. J. Pineal Res., 15, 59-69 (1993).
- Monteiro,H.P., Abdalla,D.S.P., Augusto,O. and Bechara,E.J.H., Free radical generation during δ-aminolevulinic acid auto-oxidation induction by hemoglobin and connections with porphyrinopathies. Arch. Biochem. Biophys., 271, 206-216 (1989).
- Noda,Y., Mori,A., Liburty,R. and Packer,L., Melatonin and its precursors scavenge nitric oxide. J. Pineal Res., 27, 159-164 (1999).
-
Pahernik,S.A.,
Botzlar,A.,
Hillemanns,P.,
Dellian,M.,
Kirschstein,M.,
Abels,C.,
Korell,M.,
Mueller-Hoecker,J.,
Untch,M. and
Goetz,A.E.,
Pharmacokinetics and selectivity of aminolevulinic acid-induced porphyrin synthesis in patients with cervical intra-epithelial neoplasia.
Int. J. Cancer,
78,
310-314
(1998).
10.1002/(SICI)1097-0215(19981029)78:3<310::AID-IJC9>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar
-
Palazzotti,B.,
Pani,G.,
Colavitti,R.,
De Leo,M.E.,
Bedogni,B.,
Borrello,S. and
Tommaso,G.,
Increased growth capacity of cervical-carcinoma cells over-expressing manganese superoxide dismutase.
Int. J. Cancer,
82,
145-150
(1999).
10.1002/(SICI)1097-0215(19990702)82:1<145::AID-IJC24>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- Petranka,J., Baldwin,W., Biermann,J., Jayadev,S., Barrett,J.C. and Murphy,E., The oncostatic action of melatonin in an ovarian carcinoma cell line. J. Pineal Res., 26, 129-136 (1999).
- Pieri,C., Marra,M., Moroni,F., Recchioni,R. and Marcheselli,F., Melatonin: a peroxyl radical scavenger more effective than vitamin E. Life Sci., 55, PL271-PL276 (1994).
- Pierrefiche,G. and Laborit,H., Oxygen radicals, melatonin and aging. Exp. Gerontol., 30, 213-227 (1995).
- Princ,F.G., Maxit,A.G., Gardalda,C., Battle,A. and Juknat,A.A., In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its anti-oxidant effect on the activity of haem enzymes. J. Pineal Res., 24, 1-8 (1998).
- Puy,H., Deybach,J.C., Beaudry,P., Callebert,J., Touitou,Y. and Nordmann,Y., Decreased nocturnal plasma melatonin levels in patients with recurrent acute intermittent porphyria attacks. Life Sci., 53, 621-627 (1993).
- Puy,H., Deybach,J.C., Bogdan,A., Callebert,J., Baumgartner,M., Voisin,P., Nordmann,Y. and Touitou,Y. Increased δ-aminolevulinic acid and decreased pineal melatonin production. J. clin. Invest., 97, 104-110 (1996).
- Qi, W., Reiter, R.J., Tan, D.X., Garcia, J.J., Manchester, L.C., Karbownik, M. and Calvo, J.R., Chromium (III)-induced 8-hydroxyguanosine in DNA and its reduction by anti-oxidants: comparative effects of melatonin, ascorbate and vitamin E. Environ. Hlth. Persp. 108, 399-402 (2000a).
- Qi, W., Reiter, R.J., Tan, D.X., Manchester, L.C., Siu, A.W. and Garcia, J.J., Increased levels of oxidatively damaged DNA induced by chromium (III) and H2O2: protection by melatonin and related molecules. J. Pineal Res., 29, 54-61 (2000b).
- Qi, W., Reiter, R.J., Tan, D.X., Manchester, L.C., Kim, S.J. and Garcia, J.J., Inhibitory effects of melatonin on ferric nitrilotriacetate-induced lipid peroxidation and oxidative DNA damage in the rat kidney. Toxicology, 139, 81-91 (1999).
- Reiter,R.J., Melatonin: that ubiquitously acting pineal hormone. News Physiol. Sci., 6, 223-227 1991).
- Reiter,R.J., Functional aspects of the pineal hormone melatonin in combating cell and tissue damage induced by free radicals. Europ. J. Endocrinol., 134, 412-420 (1996).
- Reiter,R.J., Anti-oxidant actions of melatonin. Adv. Pharmacol., 38, 103-117 (1997).
- Reiter,R.J., Guerrero,J.M., Garcia,J.J. and Acuna-Castroviejo,D., Reactive oxygen intermediates, molecular damage and aging: relation to melatonin. Ann. N.Y. Acad. Sci., 854, 410-424 (1998).
- Reiter,R.J., Tan,D.X., Kim,S.J., Manchester,L.C., Qi, W., Garcia, J.J., Cabrera, J.C., El-Sokkary, G. and Rouvier-Garay, V., Augmentation of indices of oxidative damage in life-long melatonin-deficient rats. Mech. Aging Develop., 110, 157-173 (1999).
- Reiter,R.J., Tan,D.X., Manchester,L.C. and Qi, W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem. Biophys., (2000). (In press).
- Shiu,S.Y., Li, L., Xu, J.N., Pang,C.S., Wong,J.T. and Pang,S.F., Melatonin-induced inhibition of proliferation and G1/S cell cycle transition delay of human choriocarcinoma JAr cells: possible involvement of MT2 (MEL1B) receptor. J. Pineal Res., 27, 183-192 (1999).
- Tan,D.X., Chen,L.D., Poeggeler,B., Manchester,L.C. and Reiter,R.J., Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocr. J., 1, 57-60 (1993).
- Tan,D.X., Manchester,L.C., Reiter,R.J., Plummer,B.F., Hardies,L.J., Weintraub,S.T., Vijayalaxmi, and Shepherd,A.M.M., A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vivo hydroxyl radical generation. Biochem. biophys. Res. Comm., 253, 614-620 (1998).
- Tan,D.X., Manchester,L.C., Reiter,R.J., Qi, W., Karbownik, M.and Calvo, J.R., Significance of melatonin in anti-oxidative defense: reactions and products. Biol. Signals Recept. (2000). (In press).
- Timmins,G.S., Liu,K.J., Bechara,E.J.H., Kotake,Y. and Swartz,H.M., Trapping of free radicals with direct in vivo EPR detection: a comparison of 5,5-dimethyl-1-pyrroline-N-oxide and 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide as spin traps for HO. and SO4.. Free Radic. Biol. Med., 27, 329-333 (1999).
- Vijayalaxmi Meltz, M.L., Reiter,R.J. and Herman,T.S., Melatonin and protection from genetic damage in blood and bone marrow: whole-body irradiation studies in mice. J. Pineal Res., 27, 221-225 (1999).