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Biomedical subjects

D P Fox

Publications and source records attributed to D P Fox.

At least 19 recordsLinked to original sources
PubMed1989

In vitro induction of chromosome damage by sulphasalazine in human lymphocytes.

Two different endpoints, sister-chromatid exchange and micronucleus induction, were measured in human peripheral blood lymphocytes stimulated to divide in short-term in vitro cultures. The cultures were exposed to sulphasalazine and 6 of its metabolites for 72 h in the absence of any exogenous metabolic activation system. Analysis of the sister-chromatid exchange and micronuclei frequencies clearly indicates that sulphasalazine itself is capable of inducing both sister-chromatid exchange and micronuclei while sulphapyridine and its acetylated metabolites only induce sister-chromatid exchange. 5-Aminosalicylic acid, the therapeutic moiety of sulphasalazine, and its acetylated metabolite did not induce either sister-chromatid exchange or micronuclei at the concentrations tested. The data from these in vitro experiments are discussed in relation to the previously reported elevations in sister-chromatid exchange and micronucleus frequencies in inflammatory bowel disease patients receiving sulphasalazine therapy.

Cells, Cultured↗
PubMed1987

The application of propidium iodide staining to the study of the macronucleus and micronuclei in the suctorian, Heliophrya sp.

Morphological changes in the macronucleus and micronuclei of the ciliated protozoon Heliophrya chapmani were investigated using the nucleic acid-specific stain propidium iodide. The fluorescence patterns of nuclei observed in propidium iodide preparations correspond well with those observed using more conventional DNA-specific methods, such as the Feulgen stain. The advantages of propidium iodide staining (minimal cell loss during staining, rapidity of the staining process, and the avoidance of cell damage during hydrolysis) make this method a quick and efficient alternative in the cytochemical study of the protozoan nucleus.

Animals↗
PubMed1985

Gamma-rays kill grasshopper primary spermatocytes in groups.

Primary spermatocyte killing by gamma-rays was studied in the grasshopper Heteracris littoralis in which spermatogenic development occurs in cysts containing a maximum of 64 cells during the first meiotic division. Cell killing at this stage is not random and mainly involves the death of whole cysts. The dose-response curve for cell killing has complex kinetics with at least two components but lacks any shoulder at low doses, thus indicating no repair of the lethal damage. Cell loss is apparent from surviving cysts as early as 45 min post irradiation but loss of greater than 24 cells is incompatible with cyst survival. Loss of fewer than 24 cells also is not random since certain values for cell loss are frequently observed while other, interspersed values are not seen at all.

Animals↗
PubMed1984

Monitoring patients on long-term drug therapy for genotoxic effects.

The problems associated with the design and conduct of experiments involving surveys of human population sister chromatid exchange (SCE) frequencies are discussed. It is suggested that the problems of variation between culture occasions may be overcome by the rigid control of experimental conditions and the inclusion of the same negative controls (herein called "base controls") on all culture occasions. In addition, all experimental subjects are cultured, as far as possible, at the same time as controls drawn from the same population and matched for age (+/- 5 yr) and sex. Many factors in such surveys remain uncontrolled but the collection of data on potential environmental mutagen exposure in all subjects is suggested as a mechanism to measure and evaluate such factors. Data are reported on SCE frequencies in lymphocytes from patients receiving 4 separate drugs for chronic conditions. Using a square root transformation of SCE frequencies and the analysis of variance, there is clear evidence for a rise in SCE frequency in patients receiving sulphasalazine (SASP) and azathioprine (Aza). On the other hand, patients receiving atenolol or chlorpropamide show no evidence of a rise in SCE frequency.

Atenolol↗
PubMed1984

Chromosome aberrations in divers.

The incidence of chromosome gain and loss and chromosomal aberrations has been measured in 48-h lymphocyte cultures of divers and control subjects as part of an overall research program to identify possible long-term health hazards associated with commercial diving. When the two diving groups, air divers (n = 77) and helium-oxygen divers (n = 76), are compared with two control groups, oil rig workers (n = 75) and nonoil industry controls (n = 52), 3.9% (6 out of 153) had an unusually high number of structural aberrations in a small portion of the dividing lymphocytes. Similar damage was not found in controls. The remaining 147 divers had a similar low incidence of chromosomal aberrations to the two control groups. The factors responsible for this phenomenon are not known, but several aspects of diving can effectively be ruled out. These are: direct effects of pressure, breathing mixture, radiographic exposure, and viral infection. The causative agent must be acting locally on lymphocytes after their last maturation division. Further studies are continuing on this topic in an effort to identify the causative factor or factors.

Air↗
PubMed1983

Increased sister-chromatid exchange frequency in patients receiving sulphasalazine therapy for ulcerative colitis.

Sister-chromatid exchange and micronucleus frequencies are reported for lymphocytes cultured in vitro from 15 patients receiving sulphasalazine therapy for ulcerative colitis and 15 controls matched for age and sex. While the patients did not differ from matched controls for micronucleus frequency there was a substantial rise in their sister-chromatid exchange frequency. This evidence of DNA damage is discussed in relation to the known cancer risk that ulcerative colitis carries and the possibility of an increased mutation rate in the germ cells of those receiving sulphasalazine therapy.

Alcohol Drinking↗
PubMed1983

Non-random chromosome loss in PHA-stimulated lymphocytes from normal individuals.

31773 lymphocyte metaphase cells from 280 karyotypically normal men aged 18-46 were examined for chromosome gain or loss. Chromosome loss was much more common than chromosome gain. Frequency of chromosome loss did not conform to a binomial distribution. There is a striking non-linear, inverse relationship between likelihood of loss and chromosome length. Chromosome gain shows a near binomial distribution between cells and no clear relationship to chromosome length. These facts indicate that the hypodiploid cells mostly arose as technical artefacts during slide preparation but that hyperdiploid cells were mainly due to non-disjunctional gain.

Adolescent↗
PubMed1981

Variation in pattern and frequency of acrocentric association in normal and trisomy-21 individuals.

Chromosomally normal and trisomy-21 individuals were studied for the ability of their nucleolus-organising chromosomes to form satellite associations in G-banded lymphocyte metaphases. Two types of parameter, absolute association frequency and relative association frequency, were used. There was no significant difference between females and males or between Caucasoids and Mongoloids for either type of association parameter in the controls, nor was there significant correlation between age (17-40 years) and either type of parameter in the controls. The pattern of two chromosome associations is accounted for by two related models in both normal and trisomic individuals. These models imply that there is an extensive polymorphism for associating ability and that this ability may be zero in individual chromosomes. Homologous do not associate preferentially with each other. The absolute frequency of acrocentric association is lower in trisomy 21 individuals than disomic controls, but the relative involvement of chromosome 21 (after correction for the trisomic state) is higher than in the controls.

Adolescent↗
PubMed1981

Correlations between relatives for acrocentric association frequency.

Acrocentric association was investigated in peripheral blood lymphocytes of twins (10 female monozygotic and 11 females dizygotic pairs), newborns and both parents (30 families), and spouses (51 pairs). Seventy two hour cultures were G-banded and scored for both absolute and relative acrocentric association frequency, except in the case of the spouse pairs where only the absolute frequency was measured. Both relative and absolute parameters of acrocentric association show positive correlations between relatives with the values being highest and most consistent in monozygotic twins, intermediate in parent and offspring, and most variable in dizygotic twins. Husband and wife pairs from our family collections show a positive correlation for the absolute parameter but not for relative parameters. The environmental factors responsible have not been identified. A rough estimate of broad sense heritability (0.81) has been made for the relative parameters. It probably contains a large component due to genetic dominance. Heritability of the absolute parameters is probably lower than for the relative parameters though estimation of its value is complicated by inconsistent results. A model is proposed to account for the variation in satellite association frequency which contains two elements: (i) The genotype determines the ratio of one chromosome type to another in the population of associated chromosomes (ii) All other environmental factors influence the absolute frequency of association without altering this basic ratio.

Adult↗
PubMed1975

Chromosome distribution in neuroblast metaphase cells of Lucusta migratoria L.

Chromosome distribution has been investigated at metaphase and C-metaphase in neuroblast cells of Locusta migratoria embryos. There is no evidence for generalised somatic association of homologues or nucleolus organising chromosomes at either stage. Homologous chromosomes 9 are found closer together than expected in C-metaphase but this seems to be due to their tendency to lie in the centre of the C-metaphase squash.

Animals↗