Advanced

Increased sensitivity to bleomycin in upper aerodigestive tract mucosa of head and neck squamous cell carcinoma patients.

Jin, Charlotte LU ; Jin, Yuesheng LU ; Wennerberg, Johan LU ; Rosenquist, Bo LU and Mertens, Fredrik LU (2008) In Mutation Research 652. p.30-37
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mutation Research
volume
652
pages
30 - 37
publisher
Elsevier
external identifiers
  • PMID:18243046
  • WOS:000255083600004
  • Scopus:40849101626
ISSN
1873-135X
DOI
10.1016/j.mrgentox.2007.12.003
language
English
LU publication?
yes
id
05a1a280-b088-460d-ba7e-9654f9d62d63 (old id 1042316)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18243046?dopt=Abstract
date added to LUP
2008-03-05 11:00:00
date last changed
2017-01-01 07:42:15
@article{05a1a280-b088-460d-ba7e-9654f9d62d63,
  abstract     = {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&lt;/=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.},
  author       = {Jin, Charlotte and Jin, Yuesheng and Wennerberg, Johan and Rosenquist, Bo and Mertens, Fredrik},
  issn         = {1873-135X},
  language     = {eng},
  pages        = {30--37},
  publisher    = {Elsevier},
  series       = {Mutation Research},
  title        = {Increased sensitivity to bleomycin in upper aerodigestive tract mucosa of head and neck squamous cell carcinoma patients.},
  url          = {http://dx.doi.org/10.1016/j.mrgentox.2007.12.003},
  volume       = {652},
  year         = {2008},
}