Effect of signal transduction inhibition in adapted lymphocytes: micronuclei frequency and DNA repair

• Published in: International journal of radiation biology 1997-03, Vol.71 (3), p.245-252
• Main Author: WOJEWODZKA, M. KRUSZEWSKI and I. SZUMIEL, M.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Adult; Biological and medical sciences; Calcium - antagonists & inhibitors; Calcium Channel Blockers - pharmacology; DNA Repair - drug effects; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Humans; Male; Micronucleus Tests; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Protein Kinase Inhibitors; Signal Transduction - drug effects; Space life sciences; Staurosporine - pharmacology; X-Rays
• ISSN: 0955-3002; 1362-3095
• DOI: 10.1080/095530097144111

Irradiation of human lymphocytes (1 cGy X rays, 37 C) or their treatment with 10 mu m hydrogen peroxide (30 min at 37 C) evoked a ca 30% decrease in the frequency of micronuclei upon subsequent X-irradiation (1.5 Gy). The response was reflected in a lower micronuclei frequency, but no change in DNA repair rate was observed as measured by the comet assay, directly after the challenge dose. Treatment of lymphocytes with staurosporine, an inhibitor of protein kinases, or with TMB-8, a calcium antagonist, carried out in parallel with the adaptive dose prevented the development of the adaptive response measured as micronuclei frequency. In lymphocytes that were staurosporine- or TMB-8-treated and irradiated under adaptive conditions showed that the rate of DNA repair was not changed. We conclude that treatment with agents that interfere with the transduction of the signal triggered by the low dose prevents the development of the adaptive response induced by X rays or hydrogen peroxide. Lower chromosome damage revealed by the cytokinesis block-micronuclei test in the adapted lymphocytes is unrelated to DNA repair rate as measured by comet assay.