Dietary modulation of mitochondrial DNA deletions and copy number after chemotherapy in rats.
Mitochondrial DNA (mtDNA) is particularly susceptible to mutation by alkylating agents, and mitochondrial damage may contribute to the efficacy and toxicity of these agents. We found that folate supplementation decreased the frequency of the "common deletion" (4.8kb, bases 8103-12,936) in liver from untreated rats and from animals treated with cyclophosphamide but not 5-fluorouracil (5-FU). The relative abundance of mitochondrial DNA was greater after chemotherapy but there was no effect of diet. Rats fed with a purified diet had fewer mitochondrial deletions than those maintained on a cereal-based diet after chemotherapy. These results indicate that diet can modulate the extent of mitochondrial damage after cancer chemotherapy, and that folic acid supplementation may be protective against mitochondrial DNA deletions.
Branda
Richard F
RF
Department of Medicine, University of Vermont, 32 N. Prospect Street, Burlington, VT 05405, USA. rbranda@zoo.uvm.edu
Brooks
Elice M
EM
Chen
Zhuan
Z
Naud
Shelly J
SJ
Nicklas
Janice A
JA
D000477:Alkylating Agents / Q000009:adverse effects; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects; D004272:DNA, Mitochondrial; D004032:Diet; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D005492:Folic Acid / Q000008:administration & dosage*; D018628:Gene Dosage; D008930:Mitochondria, Liver / Q000187:drug effects / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017384:Sequence Deletion / Q000187:drug effects*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D003520:Cyclophosphamide; D005492:Folic Acid; D005472:Fluorouracil