RESUMO
Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.
Assuntos
DNA/metabolismo , Gorduras na Dieta/toxicidade , Guanina/análogos & derivados , Fígado/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Dano ao DNA , DNA Glicosilases/biossíntese , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Enzimas Reparadoras do DNA/biossíntese , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Dieta , Gorduras na Dieta/administração & dosagem , Óleos de Peixe/administração & dosagem , Óleos de Peixe/toxicidade , Guanina/biossíntese , Guanina/metabolismo , Fígado/enzimologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Monoéster Fosfórico Hidrolases/biossíntese , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Óleo de Soja/administração & dosagem , Óleo de Soja/toxicidadeRESUMO
Oxidized dietary oils (lard, soybean oil, and sardine oil) were orally administered to C3H/HeN male mice. After 6 months, benign hepatocellular adenoma was observed in the mice treated with all three oxidized dietary oils. After 12 months, malignant hepatocellular carcinoma and hepatoblastoma were observed in addition to the benign tumor. Oxidized sardine oil caused the highest tumor incidence (35%) and malignant tumors (27.5%) among the oxidized dietary oils tested. Mice treated with oxidized lard and sardine oil exhibited a significant increase of 8-OH-dG in the livers. The amounts of 8-OH-dG found in the mice treated with oxidized sardine oil correlated with the rates of tumor incidence. After 6 months, mRNA decreased in the case of oxidized lard and sardine oil, whereas it increased in the case of oxidized soybean oil, either in 8-oxoguanine-DNA glycosylase (OGG1) or in 8-oxo-dGTPase. On the other hand, there was no appreciable change in mRNA, in either OGG1 or 8-oxo-dGTPase, after 12 months. Oxidized sardine oil contained the highest level of malonaldehyde (MA) (713+/-91.1 nmol/g) and glyoxal (33.3+/-5.2 nmol/g) among three oxidized oils. The malignant tumor incidence correlated with the high level of MA and glyoxal found in the dietary oils tested.