Genome damage in oropharyngeal cancer patients treated by radiotherapy.
OBJECTIVE
To estimate genome damage in oropharyngeal cancer patients before, during, and after radiotherapy and to measure the persistence of caused genome damage relevant in the evaluation of secondary cancer risk.


METHODS
DNA damage was evaluated in peripheral blood lymphocytes of 10 oropharyngeal cancer patients using alkaline comet assay, analysis of structural chromosome aberrations, and micronucleus assay. Blood samples were taken 2 hours before irradiation on day 1 of the first radiotherapy cycle, 2 hours after the application of the first dose, in the middle of the radiotherapy cycle, within 2 hours after the last received radiotherapy dose, and after 6 and 12 months after radiotherapy.


RESULTS
In most participants, the highest level of primary DNA damage was recorded in blood samples collected after the administration of first radiation dose (mean tail length 25.04+/-6.23 mum). Most patients also had increased frequency of comets with long tail-nucleus (LTN comets) after the administration of the first radiation dose (mean, 10.50+/-7.71 per 100 comets), which remained increased in the middle of radiotherapy (mean, 18.30+/-27.62 per 100 comets). Later on, the levels of primary DNA damage as recorded by the comet assay, slightly diminished. The frequency of structural chromosome aberrations in lymphocytes gradually increased during the radiation cycle (26.50+/-27.72 per 100 metaphases at the end of the therapy), as well as the frequency of micronuclei (mean total number of micronuclei 167.20+/-35.69 per 1000 binuclear cells).


CONCLUSIONS
Oropharyngeal cancer patients had relatively high levels of primary DNA damage in their peripheral blood lymphocytes even before therapy. The frequency of complex structural chromosome aberrations and the frequency of micronuclei increased with the progression of the radiation cycle and the doses delivered. As the frequency of chromosomal aberrations a year after radiotherapy mostly did not return to pre-therapy values, it represents an important risk factor related to the onset of second cancer.
Gamulin
Marija
M
Department of Oncology, University Hospital Center Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. marija.gamulin@zg.t-com.hr
Kopjar
Nevenka
N
Grgić
Mislav
M
Ramić
Snjezana
S
Bisof
Vesna
V
Garaj-Vrhovac
Vera
V
D000368:Aged; D002869:Chromosome Aberrations; D017523:Croatia / Q000453:epidemiology; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009959:Oropharyngeal Neoplasms / Q000453:epidemiology / Q000532:radiotherapy*; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome