Mitotic Frequency Research Articles

Changes in tumor oxygen tension during radiotherapy of uterine cervical cancer: relationships to changes in vascular density, cell density, and frequency of mitosis and apoptosis

Purpose: Changes in oxygen tension (pO 2) during the early phase of fractionated radiotherapy were studied in 22 patients with uterine cervical cancer. The aims were to investigate (a) whether possible changes in pO 2 differed among and within tumors and (b) whether the changes could be attributed to changes in vascular density, cell density, and frequency of mitosis and apoptosis. Methods and Materials: The pO 2 was measured polarographically in four regions of the tumors before treatment and after 2 weeks of radiotherapy. The vascular density, cell density, and frequency of mitosis and apoptosis were determined from biopsies taken from the tumor regions after each pO 2 measurement. Results: The changes in pO 2 during therapy differed among the tumors and were correlated to pO 2 before treatment ( p < 0.001). The direction of the changes was consistent throughout the tumors; all regions in tumors with increased oxygenation had increased or no change in pO 2 and vice versa. The tumors with increased pO 2 ( n = 10) had a large decrease in cell density and a significant increase in apoptotic frequency. In contrast, the tumors with decreased pO 2 ( n = 10) had a smaller decrease in cell density ( p = 0.014) and no significant increase in apoptotic frequency. Vascular density and mitotic frequency showed no change during therapy; however, vascular damage other than decreased vascular density was observed. Conclusion: These results indicate that the oxygenation of cervix tumors generally changes during the early phase of radiotherapy. The change depends on the balance between the factor leading to an increase and that leading to a decrease in oxygenation; i.e., decreased cell density and vascular damage, respectively. Increased apoptotic frequency may contribute to a large decrease in cell density and hence increased oxygenation during therapy.

RECURRENCE, PROGRESSION AND SUCCESS IN STAGE TA GRADE 3 BLADDER TUMORS TREATED WITH LOW DOSE BACILLUS CALMETTE-GUERIN INSTILLATIONS

Bacillus Calmette-Guerin (BCG) therapy is considered to be an effective prophylactic and therapeutic agent for high risk superficial transitional cell carcinoma of the bladder. Nevertheless, in a select uncommon population of stage Ta grade 3 superficial lamina-free tumors the results of this treatment have not yet been well established. We evaluated recurrence and progression rates, and the success of BCG therapy in a population with stage Ta grade 3 transitional cell carcinoma of the bladder. Of the 605 patients treated at our institution from 1982 to 1996 for the histopathological diagnosis of primary bladder cancer 32 (5.3%) with stage Ta grade 3 noninvasive primary bladder tumor were treated with intravesical instillations of 75 mg. Pasteur strain BCG in 50 ml. saline weekly for 6 weeks. At a followup of 2 to 13 years (mean 58.4 months) patients were evaluated with urinary cytology, cystoscopy, transurethral resection and random mucosal biopsies. Recurrence, grade and stage progression, death and causality were analyzed. Of the 32 patients 9 (28%) responded positively to BCG without recurrence, while disease recurred as stage Ta in 8 (25%) and T1 in 7 (22%), and progressed to muscle layer infiltration in 8 (25%). Four patients (12%) died of bladder cancer. The number of tumors at primary resection, gross examination, the mitotic index or an association with carcinoma in situ did not appear to be predictive factors of progression to muscle invasion. Urine cytology (I to II versus III to IV) appeared to correlate highly with progression and BCG response (p<0.001) with excellent sensitivity (1) but low specificity (0.67). Our study demonstrates the high progression potential of stage Ta grade 3 tumors, since nearly 50% recurred and 25% progressed to invasive disease. These results may be closely compared with the results of previous trials of stage T1 grade 3 disease. We suggest that recurrence should be detected at an early stage using long-term followup with strict observance of the surveillance protocols during a minimum 5-year tumor-free period.

TUMOR PROGRESSION AND SURVIVAL OF PATIENTS WITH HIGH GRADE, NONINVASIVE PAPILLARY (TaG3) BLADDER TUMORS: 15-YEAR OUTCOME

Tumor progression and survival of patients with high grade Ta bladder tumors followed for 15 to 20 years were evaluated. A total of 148 patients with Ta and 73 with T1 multiple, recurrent papillary bladder tumors were evaluated. In all patients complete transurethral resection was performed and 1 or more courses of bacillus Calmette-Guerin therapy were given. Minimum followup was 15 years. Of the Ta tumors 125 were high grade and 23 were low grade. The end points of the study were stage progression, defined as lamina propria invasion, muscle invasion or metastasis, and disease specific survival. The 15-year progression-free survival rate was 95% in the 23 patients with low grade Ta tumors and none died of disease. Progression-free survival and disease specific survival rates were 61% and 74%, respectively, in 125 patients with high grade Ta tumors compared to 44% and 62%, respectively, in 73 with T1 tumors. Patients with high grade Ta tumors have a lifelong risk of disease stage progression and death from bladder cancer similar to those with T1 tumors.

Absence of tolerance to cataleptic activity of gamma-hydroxybutyric acid after subchronic administration to male mice

The number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in stromal myofibroblasts in 125 cases of breast cancer. The mean (S.E.) of Ag-NORs in stromal myofibroblasts was 4.4 (0.1). The number of Ag-NORs in myofibroblasts was related to histological grade (p = 0.028), histological type (p = 0.013), tumour necrosis (p = 0.026), mitotic frequency (p = 0.091) and S-phase fraction (p = 0.032). The number of Ag-NORs in stromal myofibroblasts predicted survival with a borderline significance (x2 = 3.4, p = 0.052) and also in axillary lymph node negative tumours (X2 = 2.8, p = 0.095). The recurrence-free survival in the entire cohort (X2 = 7.1, p = 0.0075) and in axillary lymph node negative tumours (X2 = 7.1, p = 0.0078) could be predicted on the basis of the number of Ag-NORs in stromal myofibroblasts. In axillary lymph node positive tumours the number of Ag-NORs in stromal myofibroblasts had no prognostic value. In multivariate analysis the number of Ag-NORs in stromal myofibroblasts had no independent prognostic value.The results suggest a close interaction between stromal myofibroblasts and epithelial cancer cells in breast cancer, and stromal changes are clearly a subject for further analyses.

Nimodipine attenuates psychotigenic effects of ketamine in humans

The number of silver-stained nucleolar organizer regions (Ag-NORs) was counted in stromal myofibroblasts in 125 cases of breast cancer. The mean (S.E.) of Ag-NORs in stromal myofibroblasts was 4.4 (0.1). The number of Ag-NORs in myofibroblasts was related to histological grade (p = 0.028), histological type (p = 0.013), tumour necrosis (p = 0.026), mitotic frequency (p = 0.091) and S-phase fraction (p = 0.032). The number of Ag-NORs in stromal myofibroblasts predicted survival with a borderline significance (x2 = 3.4, p = 0.052) and also in axillary lymph node negative tumours (X2 = 2.8, p = 0.095). The recurrence-free survival in the entire cohort (X2 = 7.1, p = 0.0075) and in axillary lymph node negative tumours (X2 = 7.1, p = 0.0078) could be predicted on the basis of the number of Ag-NORs in stromal myofibroblasts. In axillary lymph node positive tumours the number of Ag-NORs in stromal myofibroblasts had no prognostic value. In multivariate analysis the number of Ag-NORs in stromal myofibroblasts had no independent prognostic value.The results suggest a close interaction between stromal myofibroblasts and epithelial cancer cells in breast cancer, and stromal changes are clearly a subject for further analyses.

Interactions between mgr, asp, and polo: asp function modulated by polo and needed to maintain the poles of monopolar and bipolar spindles.

We describe genetic interactions between mutations in mgr, asp, and polo, genes required for the correct behaviour of the spindle poles in Drosophila. The phenotype of a polo1 mgr double mutant is more similar to mgr than polo1, but the frequency of circular monopolar figures (CMFs) seen with either mutant alone is additive, suggesting that the two gene products are required for independent functions in the formation of bipolar spindles. The aspE3 mgr double mutant arrests much earlier in development than either mutant alone, indicative of a strong block to cell proliferation. We discuss whether the lack of microtubular structures in these cells reflects an extended mitotic arrest, or if it is a more direct consequence of the double mutant combination. A polo1 aspE3 double mutant shows a dramatic synergistic increase in mitotic frequency. The loss of CMFs normally associated with the polo1phenotype suggests that the Asp microtubule-associated protein is required to maintain the structure of spindle poles. We speculate that Asp protein might be a substrate for the serine-threonine protein kinase encoded by polo.

Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells.

Eukaryotic cells repair DNA double-strand breaks (DSBs) by at least two pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ). Rad54 participates in the first recombinational repair pathway while Ku proteins are involved in NHEJ. To investigate the distinctive as well as redundant roles of these two repair pathways, we analyzed the mutants RAD54(-/-), KU70(-/-) and RAD54(-/-)/KU70(-/-), generated from the chicken B-cell line DT40. We found that the NHEJ pathway plays a dominant role in repairing gamma-radiation-induced DSBs during G1-early S phase while recombinational repair is preferentially used in late S-G2 phase. RAD54(-/-)/KU70(-/-) cells were profoundly more sensitive to gamma-rays than either single mutant, indicating that the two repair pathways are complementary. Spontaneous chromosomal aberrations and cell death were observed in both RAD54(-/-) and RAD54(-/-)/KU70(-/-) cells, with RAD54(-/-)/KU70(-/-) cells exhibiting significantly higher levels of chromosomal aberrations than RAD54(-/-) cells. These observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.

Reduced X-Ray Resistance and Homologous Recombination Frequencies in a RAD54 −/− Mutant of the Chicken DT40 Cell Line

rad54 mutants of the yeast Saccharomyces cerevisiae are extremely X-ray sensitive and have decreased mitotic recombination frequencies because of a defect in double-strand break repair. A RAD54 homolog was disrupted in the chicken B cell line DT40, which undergoes immunoglobulin gene conversion and exhibits unusually high ratios of targeted to random integration after DNA transfection. Homozygous RAD54 −/−mutant clones were highly X-ray sensitive compared to wild-type cells. The rate of immunoglobulin gene conversion was 6- to 8-fold reduced, and the frequency of targeted integration was at least two orders of magnitude decreased in the mutant clones. Reexpression of the RAD54 cDNA restored radiation resistance and targeted integration activity. The reported phenotype provides the first genetic evidence of a link between double-strand break repair and homologous recombination in vertebrate cells.

Increase in the mitotic recombination frequency in Drosophila melanogaster by magnetic field exposure and its suppression by vitamin E supplement

In order to estimate possible mutagenic and/or carcinogenic activity of electromagnetic fields, wing spot tests were performed in Drosophila melanogaster. A DNA repair defective mutation mei-41 D5 was introduced into the conventional mwh/flr test system to enhance mutant spot frequency. Third instar larvae were exposed to a 5-Tesla static magnetic field for 24 h, and after molting, wings were examined under a microscope to detect hair spots with mutant morphology. The exposure caused a statistically significant enhancement of somatic recombination compared with the unexposed control. This enhancement was suppressed to the control level by supplement of vitamin E, a non-specific antioxidant. It is inferred that the magnetic field enhanced the genotoxic effect of spontaneously produced free radicals, possibly by affecting the lifetime of the radicals. Enhancement of non-disjunction, terminal deletions and gene mutations were not detected.

MTS1 gene mutations in archival oral squamous cell carcinomas.

Multiple tumor suppressor gene 1 (MTS1) has been found mutated or deleted in a variety of human cancers. Our purpose was to identify and characterize MTS1 gene mutations in primary oral squamous cell carcinomas (SCCs) in each of the three exons of the MTS1 gene. Seventeen archival samples of oral SCC were evaluated for the presence of MTS1 mutations using single strand conformation polymorphism (SSCP) and DNA sequencing. Three of 17 tumors exhibited MTS1 gene mutations: one tumor exhibited a mutation in exon 2 and two tumors exhibited mutations at the splice site junction of intron 2 and exon 3. Three tumors also exhibited a common base change in the 3' untranslated region of exon 3, which is interpreted as a likely polymorphic variant. An examination of the three tumors exhibiting MTS1 point mutations revealed no unique characteristics relative to p53 immunohistochemical activity, mitotic frequency, or degree of histologic differentiation. This study indicates that MTS1 gene mutations may be involved in at least a minor proportion of oral SCCs.

Suicide Gene Therapy for Plasma Cell Tumors

Suicide gene therapy for plasma cell tumors was attempted in severe combined immunodeficient (SCID) mice injected with human myeloma cell lines. Initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcutaneously (SC) into SCID mice could be eradicated by the administration of ganciclovir (GCV). Furthermore, an in vivo bystander effect was noticed when mice received mixtures of HSVtk-positive and nontransduced cells. Unexpectedly, a "distant bystander" effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller and had increased frequency of apoptotic figures and decreased mitotic frequency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice.

Over-expression of the NUD1-coded endo-exonuclease in Saccharomyces cerevisiae enhances DNA recombination and repair.

The NUD1(=NUC2) gene of Saccharomyces cerevisiae has been subcloned and over-expressed in multi-copy plasmids. Enhanced expression of this nuclear endo-exonuclease gene was confirmed by Northern hybridization (>10-fold increase), and increased enzymatic activity (2.4-fold increase) was demonstrated by direct immunological assay using antibody raised against the purified Neurospora crassa endo-exonuclease. We found that increased expression of NUD1 was associated with an increase in cell survival after irradiation treatment with gamma rays, and an increase in radiation-induced mitotic recombination frequencies between duplicated gene sequences. The results presented here are consistent with previous biochemical data and confirm a role for the NUD1 gene product in recombination/repair processes.

Comparison of the prognostic value of mitotic frequency and Mitotic Activity Index in breast cancer

Previous studies have shown that the Mitotic Activity Index (MAI), defined as the number of mitotic figures in 10 consecutive well-defined high power fields, is a strong and reproducible prognosticator in breast cancer. However, cellularity of tumours may vary. The Mitotic Frequency (MF), defined as the number of mitoses per a certain number of tumour nuclei, corrects for cellularity and therefore may have higher prognostic value than the MAI. The present study was undertaken to test this hypothesis by comparing the prognostic value of MAI and ME In 189 primary invasive breast cancer patients, the MAI was assessed by counting the total number of mitoses in 10 consecutive fields in the most cellular area in the periphery of the tumour. In the same fields the MF was determined by calculating the fraction of mitoses in 2000 nuclei. The time needed for the respective determinations was registered. Univariate survival analysis (Kaplan-Meier curves, Mantel-Cox test) showed that both counting methods were strong prognosticators ( P < 0.0001), but the MF was a slightly stronger prognostic factor than the MAI as reflected by the Mantel-Cox value (20.9 versus 18.1). MF and MAI showed, however, no clear differences in sensitivity, specificity, efficiency, and predictive value of positive and negative test results. In multivariate analysis, the MAI had slightly more additional prognostic value to lymph node status and tumour size. Assessment of MF took 30–45 min on average, 3 times longer than MAI assessments. In conclusion, MF and the MAI showed no marked difference with regard to prognostic value. Considering the ease and speed of MAI assessment, it remains a useful prognosticator for daily practice in management of breast cancer patients.

Dose-rate sparing for micronucleus induction in lymphocytes of controls and ataxia-telangiectasia heterozygotes exposed to 60Co gamma-irradiation in vitro.

We investigated the reproducibility of the cytochalasin B micronucleus (MN) assay in irradiated human lymphocytes to assess its suitability in predicting cancer predisposition and response to radiotherapy by virtue of defects in the processing of clastogenic lesions. G0 lymphocytes were exposed to 3.0 Gy 60Co gamma-rays at high (HDR) or low dose-rate (LDR). Six healthy donors were assayed three times each in nine experiments and compared with six ataxia-telangiectasia (A-T) heterozygotes. In controls, significant interexperiment variability in MN yields was observed at HDR and LDR, also in dose-rate sparing (i.e. reduction in MN yield at LDR compared with HDR). Significant inter-individual variability was seen at HDR, but not at LDR or for sparing. Average sparing was 66.4 +/- 4.8%. In spite of the experimental variability, a significant difference between controls and A-T heterozygotes was detected at LDR, and 5/6 heterozygotes had sparing values below the control range. This gives encouragement for the use of this assay in predictive testing if sources of experimental variability can be identified so as to improve discrimination between individuals. HDR and to a lesser extent LDR irradiation induced significant mitotic inhibition, seen as a reduction in binucleate cells after cytocholasin treatment. A positive correlation between mitotic inhibition and MN frequency suggests that similar lesions may be involved in these effects.

Primary systemic treatment with weekly doxorubicin monotherapy in women with locally advanced breast cancer; clinical experience and parameters predicting outcome.

Sixty-three patients (median age 64 years) with locally advanced breast cancer (T3, T4 and/or N2) were treated with primary 'neoadjuvant' chemotherapy given as weekly doxorubicin monotherapy (14 mg/m2 per dose). Seven patients had solitary distant metastasis at the time of diagnosis. Twenty-eight patients (45%) achieved 'partial response' to primary chemotherapy. Twenty-nine patients (46%) had 'stable disease', and 6 patients (9%) had 'progressive disease' during treatment. Following chemotherapy, 52 patients were subjected to surgery and another 4 patients had surgery performed after radiotherapy. Surgery was considered impossible in only three patients. After a median observation time of 23 months, local recurrences were observed in 2 patients, one with progressive disease and one with stable disease during chemotherapy. Univariate analyses revealed that large tumour size, high histological grade and high mitotic frequency were associated with poor primary response to chemotherapy. Recent studies have demonstrated a correlation between p53-mutations and chemotherapy response.

Quantitative histopathology in lymph node-negative breast cancer. Prognostic significance of mitotic counts.

Reliable prognostic factors are needed to improve the stratification of patients with lymph node-negative breast cancer to different therapy modalities. We investigated the prognostic value of quantitative histopathology in a retrospective study of 98 "low-risk" breast cancer patients (T1+2N0M0) with a median follow-up of 9 years. An interactive video system and stereological and morphometric techniques were used to obtain estimates of four nuclear features (mean volume, mean profile area, volume fraction, and profile density), and two mitotic counts [mitotic profile frequency (MF) and mitotic profile density (MD)]. All measurements were performed in fields of vision sampled systematically from the whole tumour area of a routine histological section. Histological grade, histological type, and oestrogen receptor (ER) status was reassessed, whereas tumour diameter and age at diagnosis were recorded from the files. We found that all quantitative histopathological variables and ER status were correlated with histological grade. Single-factor prognostic analyses showed a highly significant value of MF (2p = 0.001) and a marginally significant value of MD (2p = 0.09), whereas no other variable approached statistical significance (2p > or = 0.25). In a multivariate Cox analysis, MF was the only parameter of significant independent prognostic value (2p = 0.03). Thus, the prognostic value of nuclear features found in previous studies could not be reproduced, whereas the marked value of mitotic counts for prediction of the outcome in patients with breast cancer was confirmed. Mitotic counts are easily obtained and may be of clinical value for identification of high-risk cases among patients with lymph node-negative breast cancer.

Protection from radiation-induced chromosomal aberrations by the nitroxide Tempol.

The nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable, free radical that exhibits protection from ionizing radiation damage and from oxidative stress mediated through exposure of cells to superoxide or hydrogen peroxide. Radiation protection has been observed in both in vivo and in vitro models. To understand the mechanism of Tempol-mediated radioprotection better, the production of radiation-induced chromosome aberrations was evaluated. This study analyzed Tempol-mediated radioprotection of human peripheral blood lymphocytes (PBLs). Peripheral blood lymphocytes were exposed to control (0mM), 10 mM (Tp10), and 50 mM (Tp50) concentrations of Tempol for 20 minutes before irradiation with 0, 150, 300, and 450 cGy. One quarter ml whole blood was cultured in F12 medium and phytohemagglutinin at 37 degrees C for 49, 54, 59, and 64 hours. Colcemide was added to each sample for the last 5 hours before harvest. Cells were harvested, treated with hypotonic solution, and fixed before dropping on cold clean slides. Mitotic indices and frequency of dicentric, ring, and triradial chromosomal aberrations were determined at 1000x magnification for each treatment group at each collection point. Treatment of cells with Tempol alone did not induce the chromosomal aberration frequency above that for unirradiated controls. Radiation dose response curves for total chromosome aberration production revealed radioprotection for Tempol treatment for both 10 and 50 mM exposures. Tempol protection factors (assessed at 0.2 aberrations/cell level) for Tp 10 and Tp 50 were 2.2 and 2.8, respectively. Tempol protects against radiation-induced chromosome aberrations in human PBLs. This finding is consistent with and lends support to previous studies in which Tempol was reported to enhance cell survival and reduce radiation-induced DNA double strand breaks.

Quantitative histopathology in ductal carcinoma of the breast. Prognostic value of mean nuclear size and mitotic counts.

The prognostic value of quantitative histopathology was investigated in a retrospective study of 71 patients with ductal carcinoma of the breast. All patients were treated according to a standardized protocol. The median follow-up was 6 years. Measurements were performed in microscopic fields that were sampled systematically from the whole tumor area of a routine histologic section. The unbiased stereologic method of point-sampled intercepts was used to estimate the mean nuclear volume, [vv(nuc)]. Using a test system with points and counting frames, estimates were obtained of the mean nuclear profile area, [aH(nuc)], the nuclear volume fraction, [Vv(nuc/tis)], the nuclear profile density (ND), the mitotic profile frequency (MF), and the mitotic profile density (MD). Traditional clinicopathologic parameters and biochemical estrogen receptor status were recorded. Single-factor survival analyses were significant regarding regional lymph node status, tumor dimension, clinical stage, age, aH(nuc), and vv(nuc) (P < or = 0.03). A tendency for prognostic value of MF was found (P = 0.10), whereas Vv(nuc/tis), ND, MD, histologic grade, and estrogen receptor status were insignificant. In a multivariate Cox analysis of patients with positive lymph nodes including the variables of tumor dimension, age, ND, vv(nuc), and MF, only vv(nuc) (P = 0.01) or MF (P = 0.004) were parameters of independent prognostic value. The present feasibility study suggests that stereologic estimates of the mean nuclear volume and morphometric estimates of the mitotic profile frequency are of independent prognostic value for patients with ductal breast cancer with positive axillary lymph nodes. The prognostic information resulting from the two variables are correlated closely and cannot be separated in this study. Consequently, larger studies are needed. In addition, the independent value of quantitative histopathology in patients with lymph node negative breast cancer should be assessed.

Mitotic frequency as a prognostic factor in breast cancer

Grading of tumor malignancy in breast cancer should contribute essential information both for the prospective outcome of the individual patient as well as for TNM staging. In a series of 104 breast cancer patients we tested the prognostic validity and reproducibility of mitotic figure counting compared with TNM staging, Bloom and Richardson grading, DNA single cell cytometry, and morphometry. Four-micrometer thick hematoxylin-eosin-stained routine slides were investigated. Mitotic figures were counted in representative areas of the tumor in 10 159-μm 2—sized high power fields (HPFs) at a 400× magnification; the median value was seven and the threshold for the 25th percentile was three. This value should replace the common but prognostically invalid threshold of 10. Univariate survival analysis showed that mitotic figure counting allows the identification of three groups of patients (⩽3, 4 to 20, >20 mitoses per HPF) with significantly different survival probabilities ( P < .0001; P = .0178). Depending on the number of mitotic figures, length of survival was significantly different within the group of TIN0 tumors ( P = .0082) and the group of T1N1 or T2N0 tumors ( P = .0251). In a Cox stepwise regression model mitotic frequency counting added prognostic information to tumor size and was of higher prognostic significance than lymph node status, DNA ploidy, or mean nuclear area. The 95% confidence limit for interobserver reproducibility, tested in 20 cases, was plus/minus 8 mitoses. After quartilization an agreement of 75% was observed.

Alteration of gamma-ray-induced chromosome aberration by 0.5 M NaCl in Chinese hamster cells.

Hypertonic treatment (0.5 M NaCl in phosphate-buffered saline, pH 7.2) at 37 degrees C for 20 min slightly delayed the mitotic frequency for non-irradiated cells in G1 and G2 phases. The mitotic frequency for irradiated cells in G2 was delayed by hypertonic treatment, and that in G1 was slightly delayed by hypertonic treatment. Hypertonic treatment in non-irradiated cells did not induce any chromosomal or chromatid aberrations in either G1 or G2. Chromosomal aberrations caused by gamma-irradiation were slightly enhanced by hypertonic treatment, and chromatid aberrations were markedly enhanced by hypertonic treatment. The enhancement ratio of gamma-irradiation-induced chromatid breaks and exchanges was 1.4 and 3.0, respectively. This cell cycle dependency of chromosome aberrations induced by postirradiation hypertonic treatment was the same as that of cell survival. These findings suggested that hypertonic treatment modifies the rejoining of DNA strand breaks in G2, but slightly modifies that in G1.