Micronucleus evaluation in mitogen-stimulated lymphocytes of PUVA treated patients.
PUVA describes the treatment of patients with psoralens plus an exposure to a source of UV light of 320-400 nm (UVA). Contradictory results have been reported on the chromosomal damage of PUVA when assayed by sister chromatid exchange (SCE) method. Micronucleus (MN) test is used to detect both clastogenic (breaking) and aneugenic (abnormal segregation) effect of physical/chemical agents on the chromosomes. No data have been found on the MN formation in the cells of PUVA treated patients. Frequency of micronuclei in 72 hours cultivated/mitogen-stimulated lymphocytes of patients have been evaluated at zero time and after 20, 40, 60 sessions of PUVA treatment. While the beginning MN frequency was approximately 0.22% (n=23), it raised to approximately 0.32 (n=23), approximately 0.42 (n=14) and approximately 0.53% (n=10) corresponding respectively to 20, 40 and 60 sessions. These sessions correspond reciprocally to 54+/-23, 172+/-48, 300+/-61 joules/cm2 of UVA and 13, 26, 39 mg/kg of 8-metoxypsoralen (8-MOP). While large interindividual variances were apparent, highly significant differences have been observed between initial MN frequency and after that of the 20, 40 and 60 sessions, (p = 0.000, p = 0.004, p = 0.005, reciprocally, Wilcoxon two-related samples test). The coefficient of correlation between MN frequency and UVA doses starting from zero to 60 sessions of treatment has been found as r = 0.61. This indicates a significant relationship between UVA doses and MN frequencies. However, MN inducibility and synergistic property of 8-MOP with UVA should be taken into account. Gradual MN increase during different sessions of PUVA treatment shows that--once appeared--a part of MN at least persist in the cells of patients from a few days to a few weeks. Smoking as a confounding factor seems to increase MN frequency (p = 0.053, Mann-Whitney U-test) in the beginning population, taken as the control population. This is the first report on the kinetics of MN formation during different sessions of PUVA treatment. Based on our results, we concluded that PUVA treatment causes a detectable chromosome damaging effect on the relatively profound cells/tissues of its human users. Therapists should be careful with its use, especially on the patients who may be more susceptible to carcinogenesis (e.g. immunosuppressed and/or elderly subjects).
Hamurcu
Zuhal
Z
Medical Biology and Genetics Department, Medical Faculty, Erciyes University, 38039 Kayseri, Turkey. med-biol@erciyes.edu.tr
Demirtas
Halil
H
Ascioglu
Ozcan
O
Dönmez-Altuntas
Hamiyet
H
Aktas
Ekrem
E
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D008730:Methoxsalen / Q000009:adverse effects; D015162:Micronucleus Tests; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D011701:PUVA Therapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000009:adverse effects; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D008934:Mitogens; D017319:Photosensitizing Agents; D008730:Methoxsalen