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S M Galloway

Publications and source records attributed to S M Galloway.

85 records · Page 5Linked to original sources
PubMed1984

Sister-chromatid exchanges in association with occupational exposure to ethylene oxide.

Sister-chromatid exchange (SCE) frequencies in employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. Three worksites where the previous environmental control of ETO was known to have differed were chosen. Within these worksites, subjects were categorized into high potential exposed, low potential exposed and control groups. An additional community control group was obtained. Blood samples for chromosome studies of peripheral lymphocytes were drawn at several time points over a period of 24 months. The effects on SCE of age, sex, smoking habits and reader variation were considered. Worksites I, II and III, respectively, represented increasing levels of exposure. At Worksite III large differences among groups persisted over 24 months. At Worksite II, the SCEs in the high potential exposed workers were higher than those in the other groups. At no time was the low potential exposed group at Worksite II statistically significantly higher in mean SCE than the worksite controls. No consistent differences among groups were noted in Worksite I.

Adult↗
PubMed1984

The current status of antiobesity drugs.

The currently available antiobesity drugs will produce an additional mean weight loss of approximately 0.5 lb (0.23kg) per week for a limited period of time. There is no major difference between the weight losing properties of the various drugs, and choice of drug depends in part on other factors such as cost and side effects. Those drugs affecting catecholaminergic pathways such as phentermine and diethylpropion can be prescribed intermittently because this is as effective, cheaper and presumably less likely to result in dependence than continuing therapy. Fenfluramine however is best given continuously, the dose being built up and reduced stepwise to avoid the dangers of withdrawal depression. Individual response may depend partly upon drug compliance and metabolism but cannot be predicted except by trial and error. Once a drug is discontinued, weight regain is the rule and there is no evidence that drug therapy helps to re-educate faulty eating habits. It follows that therapy can be most easily justified if there is a short term need to achieve weight loss, e.g. prior to elective surgery. In some patients, weight regain may be prevented by giving the drug long term but the complications of long-term administration have yet to be evaluated. If it can be justified at all, it is in those subjects with complicated obesity. The development of a non-pharmacological way of preventing weight regain following drug therapy would enhance the potential usefulness of an antiobesity agent.

Adult↗
PubMed1983

Mutagenic evaluations of four rubber accelerators in a battery of in vitro mutagenic assays.

The mutagenic/carcinogenic potential of four commercial accelerators were evaluated using a battery of in vitro assays. All of these compounds were mutagenic in one or more assays. Positive responses were noted in the Escherichia coli pol A+/pol A- DNA repair, mouse lymphoma L5178Y TK+/- forward mutation, BALB/3T3 cell transformation, and CHO cell chromosome aberration assays. In contrast to previous studies of accelerators, no mutagenic response was observed in the E coli WP2 uvrA- assay or in any of the Salmonella typhimurium strains tested. These studies have indicated that rubber accelerators should be regarded as potential human health hazards and that further in vitro and in vivo studies are needed to assess the potential genetic hazards of this large class of chemicals.

Benzothiazoles↗
PubMed1980

Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains.

We have identified a group of 8 (among 39) human tumour cell strains deficient in the ability to support the growth of adenovirus 5 preparations treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but able to support the growth of non-treated adenovirus normally. This deficient behaviour defines the Mer- phenotype. Strains having the Mer- phenotype were found to arise from tumours originating in four different organs. Relative to Mer+ strains, Mer- tumour strains showed greater sensitivity to MNNG-produced killing, greater MNNG-stimulated "DNA repair synthesis and a more rapid MNNG-produced decrease in semi-conservative DNA synthesis. Here we report that (1) Mer- strains are deficient in removing O6-methylguanine (O6-MeG) from their DNA after [Me-14C]MMNG treatment (Table 1); (2) Mer- tumour strains originate from tumours arising in patients having Mer+ normal fibroblasts (Fig. 1a, b); (3) SV40 transformation of (Mer+) human fibroblasts often converts them to Mer- strains (Fig. 1c, d); (4) MNNG produces more sister chromatid exchanges (SCEs) in Mer- than in Mer+ cell strains (Fig. 2).

Adenoviruses, Human↗
PubMed1980

Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange.

Mouse embryos explanted at 7 1/2 or 8 1/2 days of gestation were cultured in medium containing benzo[a]pyrene and supplemented with 5-bromodeoxyuridine to allow detection of sister chromatid exchanges. The murine Ah locus regulates the inducible metabolism of polycyclic hydrocarbons such as benzo[a]pyrene. A high frequency of sister chromatid exchange was induced by benzo[a]pyrene in embryos from three Ah-"responsive" inbred strains (BALB/cDub, C3H/AnfCum, and C57BL/6N); there was little or no increase in two Ah-"nonresponsive" inbred strains (AKR/J and DBA/2J). Benzo[a]pyrene also induced sister chromatid exchanges in the Ah-responsive recombinant inbred line B6NXAKN-12 but not in the Ah-nonresponsive recombinant inbred line B6NXAKN-3. Sister chromatid exchange in cultured Ah-responsive mouse embryos was thus shown to be a sensitive assay. These data provide direct evidence that genetically responsive mouse embryos (early postimplantation stage) possess the subcellular processes necessary for induction of enzymes that metabolize benzo[a]pyrene to its chemically active forms(s). Both the Ah regulatory gene product (a cytoslic receptor) and the structural gene product (inducible cytochrome P1-450) therefore appear to be functional at an early embryonic age. Furthermore, this metabolic capacity may play an important role in the damage to embryonic cells by polycyclic hydracarbons.

Animals↗
PubMed1979

Vitamin C is positive in the DNA synthesis inhibition and sister-chromatid exchange tests.

Ascorbate caused a dose-dependent increase in sister-chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells and in human lymphocytes. Moreover, in the DNA synthesis inhibition test with HeLa cells, ascorbate gave results typical of DNA-damaging chemicals. Catalase reduced SCE induction by ascorbate, prevented its cytotoxicity in CHO cells, and prevented its effect on HeLa DNA synthesis. Ascorbate reduced induction of SCE in CHO cells by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by direct inactivation of MNNG.

Animals↗
PubMed1979

The relation between chemically induced sister-chromatid exchanges and chromatid breakage.

Studies of classical chromosome aberrations and sister-chromatid exchanges (SCES) suggest independent mechanisms for the two events despite some common features. Examination of chromosome breakage caused by X-rays, visible light, and viruses has shown that few chromatid breaks are accompanied by SCEs at the sites of breaks. No similar observations were available for chemically induced breaks, but it has been reported that rat chromosomes exposed to dimethylbenzanthracene (DMBA) contained a preponderance of both aberrations and SCEs in certain specific regions, implicating a common process in their formation. These conclusions were drawn from a comparison of breaks induced in vivo with SCEs induced in vitro. However, we used 7 chemical mutagens to induce both chromatid breaks and SCEs in "harlequin" chromosomes of cultured rat and Chinese hamster ovary (CHO) cells and found that 25% of the 914 breaks scored were associated with SCEs. The proportion of breaks accompanied by SCEs is related to the overall SCE frequency and falls into the range predicted on the basis that breaks and SCEs occur independently. The reported association between sites for SCEs and aberrations also reflects secondary factors, such as induction of SCEs and aberrations during DNA synthesis in late replicating regions of the chromosomes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Aneuploidy and ageing: chromosome studies on a random sample of the population using G-banding.

Chromosome analysis using G-banding was carried out on cells from 65 males and 102 females of all ages from a random sample of the population. The frequency of aneuploid cells showed a significant increase with age in both sexes, and in females the increase in hypodiploidy and hyperdiploidy was more marked than in males, and involved a high proportion of cells that had lost or gained an X chromosome, 45,X cells being much more common than 47,XXX cells. In females, the occurrence of a "fragment" of an X chromosome also correlated with increasing age, and this "fragment" appears to be an X chromosome that has simply divided prematurely at the centromere. The effects of time in culture and of repeating cultures of blood samples from the same individual on proportions of abnormal cells of various types were also investigated, and the results are discussed in the light of findings from several other "ageing surveys".

Adolescent↗
PubMed1977

Ataxia telangiectasia: the effects of chemical mutagens and x-rays on sister chromatid exchanges in blood lymphocytes.

It is now possible to examine in detail exchanges between sister chromatids (SCEs) and to attempt to investigate the relationships of such exchanges to aberration formation and DNA-repair mechanisms. The frequency of SCEs is dramatically increased by chemical mutagens and may reflect the level of DNA damage. Lymphocytes from patients with ataxia telangiectasis (AT) show high levels of spontaneous chromosome damage and are hypersentive to ionising radiations and it was of interest to examine the levels of SCE induced in these cells by various mutagens. The frequencies of SCE after treatment with X=rays or three chemical mutagens were equivalent to those in normal cells. The effects of fluorodeoxyuridine and deoxycytidine on SCE frequencies were also tested.

Ataxia Telangiectasia↗
PubMed1975

Sister chromatid exchange in human chromosomes from normal individuals and patients with ataxia telangiectasia.

A new fluorescence plus Giemsa staining technique now makes the detection of sister-chromatid exchange (SCE) a relatively easy matter in cells containing 5-BrdU-substituted DNA. The technique has been applied to human cells to examine the distribution of SCE between different people and within different chromosomes. The results show: (1) That there were no large differences in the incidence of SCE between blood leukocyte chromosomes from male and female adults and newborn, and that similar frequencies were found in cells from two patients with ataxia telangiectasia which, nevertheless, showed the typical increases in chromosomal aberrations. (2) The distribution of SCE between chromosomes in the complement was found to be proportional to chromosome length, although the smaller chromosomes were under-represented, but not significantly so. (3) The distribution of SCE within chromosomes was nonrandom, with a deficiency in the centromeric and an excess in the mid-arm regions. There was no evidence for an excess of SCE in chromosome regions rich in AT DNA sequences. (4) The frequency of SCE is to some extent dependent of 5-BrdU concentration, but the influence of concentration is minimal within the range of from 1 to 160 muM. Human cells exposed over two cell cycles at these higher BrdU levels have around 14 SCE per cell-a frequency virtually identical with that observed in cultured cells from the Chinese hamster, wallaby, and rat kangaroo.

Adult↗
PubMedDate not supplied

Chemically induced aneuploidy in mammalian cells in culture.

Our objectives were to assess whether there exist useful aneuploidy tests in vitro, to identify chemicals that showed potential for mitotic aneuploidy induction, and to recommend some features of suitable protocols for such testing. From over 100 papers we selected 24 for review. The acceptable studies examined hyperdiploidy at metaphase, had concurrent negative controls with low background rates of hyperdiploidy, used a fixation time sufficient for cells to complete more than one cell cycle after treatment and had multiple dose levels with at least 100 cells scored per point. We judged that 12 compounds were positive, 7 inconclusive, and 4 negative with the reservation that 2 of the 4 compounds had not been tested up to toxic doses. Many of the positive compounds are also known to cause structural chromosome aberrations. We separately reviewed qualitative reports of 'C-mitotic' effects, anaphase lagging, multipolar mitoses, or altered DNA content, since these effects may sometimes by associated with aneuploidy induction. No well-validated in vitro aneuploidy assay exists, and much research is required to develop tests, perhaps using chromosome counts, DNA content, or effects on cell organelles necessary for mitosis. In test protocol development we should carefully consider choice of cell sample size, use of in vitro metabolic activation systems, and selection of doses, especially with regard to the problem of whether cytotoxic concentrations should be used.

Aneuploidy↗
PubMedDate not supplied

Chromosome aberrations in individuals occupationally exposed to ethylene oxide, and in a large control population.

Chromosome aberration frequencies in 61 employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. We studied 3 worksites with differing historical ambient levels of ETO. Within worksites, groups were classified as high potential exposed, low potential exposed, or controls. Further control groups including an off-site community control group were added to give a total of 304 control individuals. Blood samples were drawn several times over a 24-month period. Aberrations were analyzed in 100 cells per sample after culture for 48-51 h. Worksites I, II and III respectively represented increasing levels of potential ETO exposure. At worksites I and II, no consistent differences in aberration frequencies were found among groups. At worksite III aberration frequencies in potentially exposed individuals were significantly increased compared with controls. The frequencies of cells with aberrations were 5.6% for the 2 individuals in the high potential exposure category and 2.6% for 23 persons in the low potential exposure group. The overall frequency of cells with aberrations in the matched control individuals was 1.4%. In the total control group of 304 individuals we found significant increases in aberrations associated with smoking and with increasing age. We have also reported previously an association between sister-chromatid exchange (SCE) frequency and ETO exposure (Stolley et al., 1984). When aberration frequencies were compared with levels of SCEs there was only a weak overall association. The correlation was found in potentially exposed but not in control groups, and for any individual, one observation could not be used to predict the other.

Adult↗