ABSTRACT
In the present study two cytogenetic parameters were used to evaluate the DNA damage induced by low doses (1 up to 40 rad) of X-ray irradiation in G0 human lymphocytes. These parameters were the frequency of chromosomal lesions in G2 and the length of this cell cycle phase. The frequency of chromosomal lesions in G2 was determined by scoring the number of chromosomal aberrations in G0 irradiated lymphocytes post treated with two inhibitors of G2 repair mechanisms: caffeine and 3-aminobenzamide. A dose-dependent increase in chromosomal aberrations yield was detected in G0 lymphocytes X-ray irradiated with or without post treatment with these two DNA repair inhibitors during G2. Nevertheless, the dose response in this latter condition was higher than the one detected in control cells, indicating that the increase of irradiation dose in G0 lymphocytes produces an increment in the number of DNA lesions arriving to be repaired in G2. The analysis of the dose-response relationships for G2 length showed an statistically significant X-ray dose-dependent increase (G2 delay) from 2.5 up to 40 rad and a positive correlation between G2 delay and the frequency of chromosomal lesions in G2. These results suggest that the DNA lesions induced by low doses of X-irradiation in G0 lymphocytes may be higher than that detected by the standard method (control conditions) and may be responsible for an increase in G2 length. We propose, therefore, that an analysis of these two cytogenetic parameters can improve the evaluation of the DNA damage induced by low doses of X-rays irradiation in G0 cells
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , DNA Damage , DNA Repair/genetics , G2 Phase/radiation effects , Lymphocytes/radiation effects , Resting Phase, Cell Cycle/radiation effects , Benzamides/pharmacology , Caffeine/pharmacology , Enzyme Inhibitors/pharmacology , G2 Phase/genetics , Lymphocytes/drug effects , Phosphodiesterase Inhibitors/pharmacology , Resting Phase, Cell Cycle/genetics , X-Rays/adverse effectsABSTRACT
A genetic approach was adopted to analyze the cell cycle G(O)(G (1) (S transition in mouse Balb/ 3T3 fibroblasts (clone A3l). We designed selection procedures to isolate revertant from the EJ-ras transformed Balb/3T3 ribroblasts that had recovered strict -control of the G(O) ( G(1), transition by serum growth factors. The aim was to uncover phenotypic traits associated with malignancy (high growth rate G(1) phase shortening and high tumorigenicity) that segregate independently.