Mitochondrial DNA mutations in the parotid gland of cigarette smokers and non-smokers.
It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations accumulate in the lung and increase in frequency with age. It has also been shown that the level of mtDNA mutations including deletions and base substitutions are elevated in lung tissue of smokers relative to non-smokers. We have previously shown that the 'common' 4977 bp mtDNA deletion is present in the parotid (salivary) gland of smokers and non-smokers and that there is a significant increase in the level of this deletion in Warthins tumour, an oncocytoma of the parotid gland. In this study we used semi-quantitative PCR to confirm the presence of 4977 bp mtDNA deletion in the parotid gland of non-smokers and smokers. Importantly, we show that the deletion accumulates with age regardless of smoking status and that there was no significant difference in the level of the 4977 bp deletion in parotid tissue of smokers and non-smokers. Using strand conformational polymorphism (SSCP) and direct sequencing we also found 5/23 smokers had parotid tissue specific base substitutions: either an A/T to G/C transition at A4767 or a G/C to A/T transition at G4853. These results are evidence of age related increase in the 4977 bp deletion and a higher level of mutations, probably due to oxidative damage, in the parotid gland of smokers.
Lewis
P D
PD
School of Biological Sciences, University of Wales Swansea, Swansea SA2 8PP, UK. p.d.lewis@swan.ac.uk
Fradley
S R
SR
Griffiths
A P
AP
Baxter
P W
PW
Parry
J M
JM
D000235:Adenolymphoma / Q000209:etiology / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010306:Parotid Gland / Q000378:metabolism*; D010307:Parotid Neoplasms / Q000209:etiology / Q000235:genetics; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
D004272:DNA, Mitochondrial; D005819:Genetic Markers