title: Numerical changes in the mitochondrial DNA displacement loop in lung lesions induced by N-nitrosobis(2-hydroxypropyl)amine in rats.
abstract: Mutations in the mitochondrial DNA (mtDNA) displacement loop (D-loop) region were investigated to clarify the possible molecular mechanisms underlying the development of lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Male Wistar rats, 6 weeks of age, were given 2000 ppm BHP in their drinking water for 12 weeks and then maintained without further treatment until sacrifice at 25 weeks. Genomic DNA was extracted from paraffin-embedded tissues and polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing, was performed. Eleven out of 24 hyperplasias (45.6%), 8 out of 16 adenomas (50.0%), and 14 out of 21 adenocarcinomas (66.7%) showed numerical changes, in a polymeric C-tract at positions 16,086-16,092 of the mtDNA D-loop, with a one base insertion of cytosine increasing the length of the C-tract, from the seven nucleotides observed in normal lung tissues from non-BHP treated rats, to eight. These changes were all homoplasmic and no changes were found in lung lesions when the length of the C-tract in the normal lung tissues adjacent to the lesions was seven. These results suggest that alterations in the mtDNA D-loop may occur in an early phase of lung carcinogenesis induced in rats by BHP.
authors.affiliation: Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Onishi
authors.forename: Mariko
authors.initials: M
authors.lastname: Saito
authors.forename: Yui
authors.initials: Y
authors.lastname: Sokuza
authors.forename: Chiharu
authors.initials: C
authors.lastname: Mori
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugata
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics; D000236:Adenoma / Q000139:chemically induced / Q000235:genetics; D000818:Animals; D004272:DNA, Mitochondrial / Q000187:drug effects*; D006965:Hyperplasia / Q000139:chemically induced / Q000235:genetics; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D009602:Nitrosamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004272:DNA, Mitochondrial; D009153:Mutagens; D009602:Nitrosamines; C012457:diisopropanolnitrosamine