PMID- 18243046
OWN - NLM
STAT- MEDLINE
DCOM- 20080528
LR  - 20191210
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 652
IP  - 1
DP  - 2008 Mar 29
TI  - Increased sensitivity to bleomycin in upper aerodigestive tract mucosa of head 
      and neck squamous cell carcinoma patients.
PG  - 30-7
LID - 10.1016/j.mrgentox.2007.12.003 [doi]
AB  - Previous studies on lymphocytes have suggested that patients with head and neck 
      squamous cell carcinoma (HNSCC) have an increased susceptibility for chromosomal 
      damage induced by bleomycin, a known radiomimetic mutagen. However, it has so far 
      not been possible to study whether this genetic instability is present also in 
      the epithelial component of the upper aerodigestive tract mucosa, the tissue from 
      which HNSCC originates. In the present study, we have successfully cultured 
      epithelial cells and fibroblasts isolated from non-neoplastic mucosa samples of 
      30 HNSCC patients and 56 controls. All cell cultures were exposed to bleomycin 
      and chromosome instability was assessed by analysis of chromosome breakage in 
      cells harvested after 2h of exposure and subsequent removal of bleomycin. 
      Furthermore, the status of the fragile histidine triad gene (FHIT) in chromosome 
      band 3p14.2 was studied by fluorescence in situ hybridization (FISH) in 
      epithelial cells that had been cultured after removal of bleomycin. Chromosomal 
      damage, in the form of chromosomal breaks and gaps, was seen in all cell cultures 
      harvested 2h after exposure to bleomycin. In epithelial cells, the frequency of 
      chromosome breakage was significantly higher among HNSCC patients than among 
      controls [mean breaks per cell (b/c) 1.02 vs. 0.77, p=0.02]. When subdivided 
      according to smoking status, age, and sex, a significantly higher frequency of 
      chromosome breakage was still found in HNSCC patients (smokers, p=0.01, age</=70 
      group, p=0.03, male, p=0.02). However, no significant difference was found 
      between fibroblasts from HNSCC patients and controls (b/c 1.21 vs. 1.23). In the 
      cell cultures growing after termination of bleomycin exposure, the frequency of 
      chromosome breakage was generally very low and no significant difference could be 
      found between the HNSCC patients and controls when epithelial cells were 
      examined. In subcultured fibroblasts, a higher frequency was found in HNSCC 
      patients than in controls (b/c 0.59 vs. 0.19, p=0.03). Interphase FISH on 
      cultured epithelial cells from HNSCC patients (n=10) and controls (n=12) showed 
      that the frequency of FHIT deletion was significantly higher in HNSCC patients 
      than in controls. Our results support the notion that HNSCC patients accumulate 
      genetic damage more rapidly, possibly due to an inherent susceptibility, which 
      could explain the high risk for multi-focal neoplastic cell transformation.
FAU - Jin, Charlotte
AU  - Jin C
AD  - Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. 
      charlotte.jin@med.lu.se <charlotte.jin@med.lu.se>
FAU - Jin, Yuesheng
AU  - Jin Y
FAU - Wennerberg, Johan
AU  - Wennerberg J
FAU - Rosenquist, Bo
AU  - Rosenquist B
FAU - Mertens, Fredrik
AU  - Mertens F
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071217
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (fragile histidine triad protein)
RN  - 11056-06-7 (Bleomycin)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
SB  - IM
MH  - Acid Anhydride Hydrolases/genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Algorithms
MH  - Antibiotics, Antineoplastic/adverse effects
MH  - Bleomycin/*adverse effects
MH  - Carcinoma, Squamous Cell/*pathology
MH  - Cells, Cultured
MH  - Epithelial Cells/drug effects
MH  - Female
MH  - Fibroblasts/drug effects
MH  - Gastric Mucosa/*drug effects/pathology
MH  - Gene Deletion
MH  - Head and Neck Neoplasms/*pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Models, Biological
MH  - Mouth Mucosa/*drug effects/pathology
MH  - Mutagenicity Tests
MH  - Neoplasm Proteins/genetics
MH  - Respiratory Mucosa/*drug effects/pathology
EDAT- 2008/02/05 09:00
MHDA- 2008/05/29 09:00
CRDT- 2008/02/05 09:00
PHST- 2007/05/03 00:00 [received]
PHST- 2007/11/26 00:00 [revised]
PHST- 2007/12/03 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/05/29 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - S1383-5718(07)00363-4 [pii]
AID - 10.1016/j.mrgentox.2007.12.003 [doi]
PST - ppublish
SO  - Mutat Res. 2008 Mar 29;652(1):30-7. doi: 10.1016/j.mrgentox.2007.12.003. Epub 
      2007 Dec 17.