Increase in DNA polymerase gamma in the hearts of adriamycin-administered rats.
It is hypothesized that the cause of myocardiopathy is oxidative damage to mitochondrial DNA. To clarify this hypothesis, DNA polymerase gamma activity, which is related to the final step of mitochondrial DNA repair or renewal, was measured. One cycle of treatment consisted of five injections of adriamycin over 5 days at a dose of 1 mg/kg of body weight per day and then 2 days resting time. DNA polymerase gamma activities in the heart after one cycle of treatment were lower than the control level. However, DNA polymerase gamma activities increased with continued adriamycin treatment, reaching a maximum level in the heart at 14 days after two cycles of adriamycin treatment. Induction of DNA polymerase gamma activity was found in rat heart following three and four cycles of administration. Under these conditions, it is doubtful that mitochondrial DNA is the direct target of adriamycin administration. The damaged mitochondrial DNA may be protected by actions of the renewal or repair systems, maintaining mitochondrial function in the heart. Rat hearts at 7 days after one cycle of adriamycin treatment show morphological changes in the mitochondria that include matrix swelling and cristae disorganization, as seen in cardiac cells by electron microscopy; however, 28 days after treatment, the mitochondria appear to have recovered.
Ogihara
Mari
M
Department of Nuclear Medicine and Radiological Sciences, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Tanno
Munehiko
M
Izumiyama
Naotaka
N
Nakamura
Hiroaki
H
Taguchi
Takahiko
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000074002:DNA Polymerase gamma; D004261:DNA Replication / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000302:isolation & purification / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D004317:Doxorubicin; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase