TY - JOUR
T1 - Comparison of the protective effect of melatonin with other antioxidants in the hamster kidney model of estradiol-induced DNA damage
AU - Karbownik, Małgorzata
AU - Reiter, Russel J.
AU - Cabrera, Javier
AU - Garcia, Joaquin J.
N1 - Funding Information:
Research was supported by a grant from Amoun Pharmaceutical Company.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - 17β-Estradiol (E2) is a known carcinogen. Estrogen induction of tumors in hamster kidney is a model of estrogen-related carcinogenesis. Melatonin is a well-known antioxidant, free radical scavenger and oncostatic agent. Changes in the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), an index of DNA damage, were measured in kidneys, liver and testes from hamsters treated with E2 (75 mg/kg b.w.) and collected 5h later. Potential protective effects of melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA) and ascorbic acid (AA) against E2-induced DNA damage were tested. The antioxidants were applied in equimolar doses of 64.5 μmol/kg b.w., 2 and 0.5 h before and 2 and 4 h after E2 treatment. E2 treatment caused a significant increase in 8-oxodGuo levels in kidneys, but did not influence significantly the oxidation of guanine bases in liver and testes. Melatonin, IPA and AA, but not NAS, completely prevented E2-induced DNA damage in hamster kidneys. It is concluded that melatonin, IPA and AA may be effective in protecting against E2-related DNA damage and, consequently, carcinogenesis.
AB - 17β-Estradiol (E2) is a known carcinogen. Estrogen induction of tumors in hamster kidney is a model of estrogen-related carcinogenesis. Melatonin is a well-known antioxidant, free radical scavenger and oncostatic agent. Changes in the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo), an index of DNA damage, were measured in kidneys, liver and testes from hamsters treated with E2 (75 mg/kg b.w.) and collected 5h later. Potential protective effects of melatonin, N-acetylserotonin (NAS), indole-3-propionic acid (IPA) and ascorbic acid (AA) against E2-induced DNA damage were tested. The antioxidants were applied in equimolar doses of 64.5 μmol/kg b.w., 2 and 0.5 h before and 2 and 4 h after E2 treatment. E2 treatment caused a significant increase in 8-oxodGuo levels in kidneys, but did not influence significantly the oxidation of guanine bases in liver and testes. Melatonin, IPA and AA, but not NAS, completely prevented E2-induced DNA damage in hamster kidneys. It is concluded that melatonin, IPA and AA may be effective in protecting against E2-related DNA damage and, consequently, carcinogenesis.
KW - 17β-Estradiol
KW - Antioxidants
KW - DNA damage
KW - Hamster kidney
KW - Melatonin
UR - https://www.scopus.com/pages/publications/0035283408
UR - https://www.scopus.com/pages/publications/0035283408#tab=citedBy
U2 - 10.1016/S0027-5107(00)00164-0
DO - 10.1016/S0027-5107(00)00164-0
M3 - Article
C2 - 11239965
AN - SCOPUS:0035283408
SN - 0027-5107
VL - 474
SP - 87
EP - 92
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -