Detection of hypoxia by measurement of DNA damage and repair in human lymphocytes (comet assay): a predictive variable for tumor response during chemotherapy in patients with head and neck squamous cell carcinoma.
BACKGROUND
Only few studies have tried to identify parameters at the time of diagnosis or during treatment that can assist the clinician in predicting the response to Cisplatin, 5-Fluorouracil +/- Folinic acid therapy in patients with head and neck squamous cell carcinoma (HNSCC).


METHODS
The alkaline comet assay was used to measure both cellular hypoxia and DNA single-strand break (ssb) kinetics in individual lymphocytes of HNSCC patients undergoing combined therapy. The intracellular level of FdUMP, dUMP and mTHF were also measured during treatment.


RESULTS
Two distinct types of cell populations were detected, from the less damaged population representing the hypoxic cells to the most damaged cells population representing the aerobic cells. We also described a direct relationship between DNA damage and repair and drug metabolism in lymphocytes and treatment efficacy.


CONCLUSIONS
The response of tumors to chemotherapy is thought to be a function of the drug's pharmacological properties (the intracellular level of FdUMP and mTHF). In addition, a relationship between platinum DNA adduct levels in lymphocytes DNA (comet assay) and tumor response has been observed, suggesting that clinical resistance to platinum drugs is attributable to DNA repair functions of the host, and thus the degree of cytotoxicity is similar across all cell types.
Romanet
T
T
Laboratory of Pharmacology, University Hospital, Grenoble, France.
Ré
J L
JL
De Méo
M
M
Serre-Debeauvlais
F
F
Lavieille
J P
JP
Reyt
E
E
Riva
C
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D015687:Cell Hypoxia / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D005468:Fluorodeoxyuridylate / Q000378:metabolism; D005472:Fluorouracil / Q000627:therapeutic use; D005492:Folic Acid / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D002955:Leucovorin / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D011237:Predictive Value of Tests; D013938:Thymidine Monophosphate / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D003856:Deoxyuracil Nucleotides; D005468:Fluorodeoxyuridylate; D013938:Thymidine Monophosphate; D005492:Folic Acid; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil