Mean Mutant Frequency Research Articles

Sister chromatid exchange frequency in Hodgkin's disease patients with elevated in vivo hprt mutant frequencies

The frequency of sister chromatid exchanges (SCEs) was determined in Hodgkin's disease (HD) patients prior to therapy, following radiotherapy, and following combined radiotherapy and chemotherapy. The frequency of hprt- mutants in these patients has been reported previously. The frequency of SCEs and hprt- mutants in the same individuals were compared. In non-HD controls the mean SCE frequency and the mean of high SCE frequency cells (HFCs) were significantly increased by smoking, while mutant frequency (MF) showed no effect. Untreated HD patients had mean SCEs, mean HFCs and mean MFs that were higher than non-MD controls. In treated patients, mean SCE and HFC frequencies were lower than untreated patients and non-HD controls, while their MFs were significantly elevated. Overall, SCE frequency was not correlated with MF in control or HD patient groups, suggesting that these biomarkers may reflect, in this case, fundamental biological differences between these processes.

In vivo hprt mutant frequencies in T-cells of normal human newborns

Mutation at the hypoxanthine-guanine phosphoribosyl transferase locus ( hprt; HPRT enzyme) in the human fetus was studied by clonal assay of placental cord blood samples from full-term newborns. Conditions for determining hprt mutant frequencies, as defined for adults, were also optimal for studies in newborns. The mean mutant frequency for 45 normal human newborns (37 male, 8 female) was 0.64 × 10 −6 (SD = 0.41 × 10 −6; median value = 0.58 × 10 −6). These values are approx. 10-fold lower than corresponding adult hprt mutant frequency values. Factors such as limiting-dilution cloning efficiencies, delay prior to study of sample, sex, cryopreservation or technician performing the assay did not significantly affect assay results. Maternal smoking did not result in elevated mutant frequency values. Most wild-type and mutant clones studied were CD4 surface antigen positive (helper/inducer). All hprt mutants analyzed lacked HPRT activity.

In vivo mutant T cell frequency in atomic bomb survivors carrying outlying values of chromosome aberration frequencies

Frequencies of HPRT − mutant T cells were determined by means of a direct clonal assay in atomic bomb survivors who showed outlaying values of chromosome aberration frequencies. The studied survivors consisted of 2 groups: those whose aberration frequency was near the higher end of the distribution (high-aberration group) and those whose aberration frequency was near the lower end of the distribution (low-aberration group). The mean radiation doses (T65D) of the high-aberration group (13 people) and low-aberration group (17 people) were 248 and 273 rad, respectively. The mean mutant frequency (Mf) of the high-aberration group was 6.7 × 10 −6, which was significantly higher than that of the low-aberration group (3.7 × 10 −6) or that of 17 controls (3.4 × 10 −6). When all the samples were combined, the correlation between Mf and radiation dose was not significant using either dose estimation system, T65D or DS86. However, the correlation coefficient was higher when DS86 doses were used. Mf correlated significantly with increasing aberration frequencies. The tendency that Mf correlates better with chromosome aberration frequency than with estimated radiation dose was stronger in this study than in a previous study where the samples were selected randomly.

Increased somatic cell mutant frequency in atomic bomb survivors

Frequencies of mutant T-cells in peripheral blood, which are deficient in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity, were determined for atomic bomb survivors by direct clonal assay using a previously reported method (Hakoda et al., 1987). Results from 30 exposed survivors (more than 1 rad exposed) and 17 age- and sex-matched controls (less than 1 rad exposed) were analyzed. The mean mutant frequency (Mf) in the exposed (5.2 × 10 −6; range 0.8−14.4 × 10 −6) was significantly higher than in controls (3.4 × 10 −6; range 1.3−9.3 × 10 −6), which was not attributable to a difference in non-mutant cell-cloning efficiencies between the 2 groups, which were virtually identical. An initial analysis of the data did not reveal a significant correlation between individual Mfs and individual radiation dose estimates when the latter were defined by the original, tentative estimates (T65D), even through there was a significant positive correlation of Mfs with individual frequency of lymphocytes bearing chromosome aberrations. However, reanalysis using the newer revised individual dose estimates (DS86) for 27 exposed survivors and 17 controls did reveal a significant but shallow positive correlation between T-cell Mf values and individual exposure doses. These results indicate that HPRT mutation in vivo in human T-cells could be detected in these survivors 40 years after the presumed mutational event.

Mutagenicity monitoring in humans by autoradiographic assay for mutant T lymphocytes

Somatic cell mutation which occurs in vivo in humans can be determined by measurement of the frequency of the 6-thioguanine-resistant (TG r) T lymphocytes in samples of peripheral blood. This frequency can be determined by either a short-term autoradiographic methodology or a longer cell-cloning methodology. The advantage of the former is the relative simplicity of the assay, while the latter allows recovery of mutant clones for further characterization. This report presents results of a longitudinal study of cancer chemotherapy nurses and other health care personnel by use of the autoradiography assay. The use of this assay in human mutagenicity monitoring and the analysis of the TG r cell frequencies are discussed in terms of age effects and validation of ‘elevated’ frequencies by use of the clonal assay. This report then presents evidence that both assays yield similar TG r cell frequencies in two groups of ‘normal adults’. The mean variant frequency (± S.D.) for 82 autoradiographic assays was 8.7 (± 6.1) × 10 −6, while the mean mutant frequency (± S.D.) for 115 clonal assays was 6.5 (± 4.8) × 10 −6. In addition, concurrent autoradiographic and clonal assays on 33 individuals yielded mean values (± S.D.) of 8.4 (± 8.5) × 10 −6 and 10.5 (± 6.3) × 10 −6, respectively.

Mitogenic stimulation may induce an anti-mutagenic repair system in human lymphocytes

The effect of mitogenic stimulation prior to X-irradiation was studied in human lymphocytes using a cloning technique. The hypoxanthine phosphoribosyltransferase locus was monitored and mutant cells were selected by their ability to form a clone in the presence of 6-thioguanine. Survival and mutagenesis were studied for cells irradiated before phytohaemagglutinin (PHA) stimulation and 1-7 days after PHA stimulation. Prior mitogenic stimulation had no effect on the decreasing survival observed with increasing X-ray dose. The mean mutation frequency of unirradiated cells ranged from 1.8 x 10(-6) to 3.3 x 10(-6). Cells irradiated and then stimulated with PHA showed an increase in mutation frequency with increasing dose of X-rays, up to 9.5 x 10(-5) after 400 rad, but mitogenic stimulation with PHA on days 2 or 3 before irradiation completely, and on days 1, 5 or 7 almost completely, prevented induction of mutations by 300 rad. These results suggest that mitogenic stimulation activates an anti-mutagenic system which prevents pre-mutational lesions produced by X-irradiation being transformed into mutations. The lack of effect of PHA stimulation on survival suggests that the types of damage leading to mutations and lethality are different.

Mutations in human lymphocytes: Effect of X- and UV-irradiation

The mutagenic effects of X- and UV-irradiation on human lymphocytes were studied using a highly efficient cloning technique. The hypoxanthine-guanine phosphoribosyl-transferase enzyme locus was used to study mutation induction, with mutant cells being selected by their ability to form a clone in the presence of the purine analogue 6-thioguanine. Mutation dose-response curves for X- and UV-irradiation were established by studying lymphocytes from 11 individuals on day 10 after irradiation. The mean mutation frequency of unirradiated lymphocytes was 2.9 × 10 −6 and there were dose-dependent increase to 9.5 × 10 −5 after 400 rad of X-irradiation, and to 5.6 × 10 −5 after 125 erg/mm 2 of UV. The expression time of X-ray-induced mutations was 3−7 days. Dose-responses were obtained for mutation frequency and survival following X-irradiation of proliferating and non-proliferating lymphocytes from 8 individuals. Compared with non-proliferating lymphocytes, the proliferating lymphocytes developed fewer mutations but had a greater mortality after irradiation.

Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa: I. Development of isogenic strains and spontaneous mutability

7 different mutations that confer sensitivity to inactivation by ultraviolet light have been investigated for their effect on spontaneous mutation at the ad-3A and ad-3B loci in haploid strains of Neurospora crassa. The collection and development of strains isogenic to wild-type 74A is described as well as experiments to determine the effects of each mutation on the spontaneous ad-3 mutation frequency. 6 of the strains showed spontaneous ad-3 mutant frequencies not significantly different from the wild-type strain. Strain uvs-3 is highly mutable spontaneously with marked variation from experiment to experiment; the mean mutation frequency in this strain in about 40-fold higher than that found in the wild-type strain.