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J M Parry

Publications and source records attributed to J M Parry.

At least 73 records · Page 4Linked to original sources
PubMed1998

How might general practitioner knowledge of patient Helicobacter pylori status change the management of dyspepsia in primary care?

BACKGROUND: Recent guidelines have suggested that testing young dyspeptic patients for Helicobacter pylori infection will produce more appropriate referrals for endoscopic investigation. Our aim was to describe how awareness of patient H. pylori status changes the practice of general practitioners (GPs) who do not currently use H. pylori testing and/or eradication in their management of dyspepsia. We studied a 5 per cent systematic sample (n = 177), stratified by health authority, of GPs in the North West region of England. METHODS: A questionnaire-based assessment of self-reported practice of young patients with dyspepsia was carried out. RESULTS: Over three-quarters of GPs would choose eradication therapy rather than ulcer healing drugs if they knew the patient was positive for H. pylori infection. Twenty-nine per cent of GPs would refer for endoscopy when the patient's H. pylori status was unknown, 32 per cent when it was positive, and 22 per cent when it was negative. However, GPs responded in an inconsistent manner to knowledge of patient H. pylori status. Some chose to refer positive patients only, others only patients with negative status, and a minority would refer both positive and negative patients. CONCLUSIONS: Until the use of H. pylori tests in primary care populations has been evaluated in appropriate prospective randomized controlled trials, advocates of testing as a means to reduce endoscopy referrals should be cautious about its potential impact on service workload.

Clinical Competence↗
PubMed1998

Testing for Helicobacter pylori in primary care: trouble in store?

STUDY OBJECTIVE: To assess the role of testing for Helicobacter pylori in the management of dyspeptic patients in primary care. DESIGN: Selective review of literature frequently quoted to support use of H pylori testing. MAIN RESULTS: Testing for H pylori and referral of only positive cases for endoscopy aims to reduce the number of "unnecessary" endoscopies. Patients with negative results may receive short-term reassurance and subsequently place fewer demands on health services. However, studies to date have only assessed this practice in secondary care settings. Given the relatively high prevalence of both dyspepsia and H pylori infection, the transfer of this practice to primary care may lead to a paradoxical increase in endoscopy referrals. Identification of H pylori and prescribing of eradication treatment also aims to reduce endoscopy referrals. No primary care trials have yet assessed this approach. Given that fewer than one in four of dyspeptic patients have peptic ulceration, a high proportion may fail to respond to eradication treatment and subsequently require referral for endoscopy. The longer term clinical and psychosocial sequelae of treating or labelling patients with an infection associated with gastric cancer remain unknown. CONCLUSIONS: Given uncertainty concerning the possible adverse effects of H pylori testing in primary care, we suggest a moratorium on its use in this setting until results from relevant clinical trials become available.

Aged↗
PubMed1998

Application of the restriction site mutation technique to N-methyl-N-nitrosourea-induced mutations in the rat.

The restriction site mutation (RSM) assay was developed in this laboratory for the detection of point mutations that occur within restriction endonuclease recognition sequences in the genomic DNA of the rat. Mutations were detected and identified in a number of tissues from N-methyl-N-nitrosourea (MNU)-treated rats. Resistant restriction enzyme products were detected in 5 of the 13 restriction endonuclease recognition sequences tested (NcoI, BslI, CfoI, DdeI, and HindIII). These mutations were detected in the p53 tumor suppressor gene and the H-ras protooncogene. No resistant RSM products were detected in any of the samples taken from untreated animals. The MNU-induced mutations were identified as G to A and A to G transitions. Our results describe the first successful application of the RSM assay in detecting induced mutations in the rat and highlight the usefulness of the RSM assay in the analysis of mutagen-induced base changes without the requirement for selection of a mutant phenotype. Given the increasing use of the rat as an animal model in genotoxicity studies, the development of such tests is essential for future genotoxicity investigations.

Animals↗
PubMed1997

Thalidomide: lack of mutagenic activity across phyla and genetic endpoints.

The human and rabbit teratogen thalidomide has been tested for mutagenicity in a wide range of assays, ranging from bacterial gene mutation assays conducted in vitro to in vivo cytogenetic assays conducted using rabbits, and including a variety of human-derived tissues. Thalidomide was not mutagenic to 6 strains of Salmonella when tested both in the presence and absence of Aroclor-induced rat liver S9 mix. This inactivity was confirmed in strains TA98 and TA100 using a 1-h pre-incubation assay protocol with the same S9 mix (10% S9), and additionally, in strain TA98 using 3 concentrations of S9 (4%, 10% and 30% S9 in S9 mix). Thalidomide was not clastogenic either to cultured human lymphocytes (whole blood cultures, minus S9 mix) or to Chinese hamster ovary (CHO) cells treated in vitro. Further, no cytotoxicity was observed in purified human lymphocytes when exposed to thalidomide up to the limit of its solubility in the medium in the presence and absence of liver S9 from Aroclor-induced pregnant rabbit. The CHO assays were conducted without metabolic activation and in the presence of a variety of sources of auxiliary metabolic activation (PB/beta NP-induced rat liver S9 mix, pooled male and female human liver S9 mix, uninduced and Aroclor-induced pregnant rabbit liver S9 mix and foetal rabbit S9 mix). Thalidomide did not induce micronuclei in isolated human lymphocytes (minus S9 mix) and it was non-mutagenic to mouse lymphoma L5178Y TK+/- cells when tested to the limits of its solubility in the culture medium (+/- S9 mix). No indication of recombinogenic or clastogenic activity was observed for thalidomide when tested in Drosophila. In addition, it failed to induce chromosome aberrations in grasshopper neuroblasts when tested in the presence and absence of Aroclor-induced rat liver S9 mix. Some unusual chromosome morphologies were observed in the grasshopper cytogenetic preparations indicating a potential of thalidomide to interact with chromosomal proteins. However, this potential was not evident in the human lymphocyte micronucleus assay, and thalidomide was apparently not reactive to the proteins of the mouse skin, as it gave negative results in a mouse local lymph node assay for skin sensitizing agents. Thalidomide was inactive in bone marrow micronucleus assays conducted using males and females from two strains of mice, and female New Zealand white rabbits. It is concluded that thalidomide is neither a mutagen nor an aneugen. This conclusion is discussed within the context of the results of earlier mutagenicity studies, the recent claim that thalidomide may be a heritable germ cell mutagen to humans, and the current interest in thalidomide for the treatment of immune system-related diseases.

Abnormalities, Drug-Induced↗
PubMed1997

The application of the 32P-postlabelling assay to aquatic biomonitoring.

The aquatic environment is known to contain a variety of natural and anthropogenic compounds that are capable of interacting with the genetic material of aquatic organisms. The increases in the levels of these anthropogenic contaminants, associated with widespread industrialisation, has led to the requirement for reliable methodologies to monitor their potential impact upon exposed aquatic organisms. Of the molecular techniques currently available, the 32P-postlabelling assay for the detection of DNA adducts offers considerable potential for the qualitative and quantitative assessment of genotoxin exposure. Here we describe several studies in which the technique was adapted for evaluation in two marine bioindicator species the common mussel Mytilus edulis and the flatfish Limanda limanda. Laboratory studies in which M. edulis specimens were exposed to 2-aminofluorene and 4-nitroquinoline 1-oxide confirmed the species' capacity to form genotoxin-related adducts. However, in further studies, no exposure-related adducts could be detected in M. edulis specimens placed in mesocosms containing environmentally realistic levels of anthropogenic contaminants. Biologically significant levels of adducts were detected in L. limanda specimens exposed to sediment bound contaminants under controlled conditions, although the levels did not appear to be statistically significant. An in situ study in which adduct levels were determined in L. limanda specimens from two sites of contrasting contamination levels proved to be more conclusive. The results were both biologically and statistically significant, suggesting that adduct levels could well be related to the levels of sediment-bound contaminants. Together the studies confirmed that the determination of the levels of DNA adducts could be used as indicators of the exposure of aquatic organisms to environmental genotoxins.

Animals↗
PubMed1997

Comparative induction of micronuclei in repair-deficient and -proficient Chinese hamster cell lines following clastogen or aneugen exposures.

The Chinese hamster cell line V79-4 and two ionising radiation-sensitive mutants irs1 and irs3, were used to assess the genotoxic effects of a clastogen (X-rays), an aneugen (podophyllotoxin) and an agent having both activities (etoposide), using the cytokinesis-block micronucleus assay combined with kinetochore labelling. All three agents induced micronuclei in a dose-dependent manner. Between 70 and 90% of the micronuclei induced by X-rays were kinetochore-negative and indicative of clastogenic activity, the relative frequencies of which were increased in the repair-deficient cell lines. In contrast, podophyllotoxin induced mainly kinetochore-positive micronuclei (up to 97%) and could be classified as an inducer of chromosome lagging and was essentially aneugenic in its activity. Micronuclei induced by etoposide were 61-84% kinetochore-negative and 26-39% kinetochore-positive, indicating both clastogenic and aneugenic activity. In the case of both etoposide and podophyllotoxin, there were no observed differences in the induction of micronuclei between the wild-type and repair-deficient cell lines. The data demonstrate the effectiveness of the cytokinesis-block micronucleus/kinetochore assay in determining the mechanisms of action of both chemicals and radiations upon chromosome structure and number and the potential influences of repair upon micronuclei induction.

Aneuploidy↗
PubMed1997

An initial assessment of the genotoxic impact of the Sea Empress oil spill by the measurement of DNA adduct levels in the intertidal teleost Lipophrys pholis.

The Sea Empress oil spill resulted in the release of vast quantities of potentially genotoxic contaminants into the coastal environment of the county of Pembrokeshire (UK). We are at present attempting to determine the potential genotoxic impact of the incident upon the native marine species of the area. Here we describe the levels of DNA adducts in specimens of the intertidal teleost, Lipophrys pholis, exposed to extensive oil extensive oil contamination as an indication of exposure to potential genotoxins. We detected elevated levels of adducts in L. pholis specimens from an area that underwent heavy oil contamination as compared to specimens from a clean reference area devoid of oil contamination. These preliminary studies indicated that the oil contamination induced DNA adducts in the L. pholis specimens, which could potentially cause genetic damage in this native marine species. Further studies are now required to assess the full extent of the genotoxic impact of the oil spill upon the Pembrokeshire area's native marine life.

Animals↗
PubMed1997

Enhanced restriction site mutation (RSM) analysis of 1,2-dimethylhydrazine induced mutations, using endogenous p53 intron sequences.

The restriction site mutation (RSM) assay was used to study the mutational sensitivities of three target regions of the murine p53 gene. The non-coding intron 6 target region was compared with the coding regions exon 4 and exon 5 with respect to their relative sensitivity to the induction of mutations by 1,2-dimethylhydrazine (DMH). Our results demonstrated that the majority of induced mutations detected were in the intron 6 gene region. A total of 15 enzyme-resistant restriction sites were detected in DMH treated mice, nine of these in the intron 6 region, four in the exon 4 region and two in the exon 5 region. The elevated sensitivity of the intron 6 region was exemplified by our detection of spontaneous mutations in this region; two resistant restriction sites were detected in untreated animals. No spontaneous mutations were detected in either of the exon sequences studied here, nor have any been detected in exon targets in our previous in vivo RSM analyses. The mutations induced by DMH were mostly GC-->AT transitions, as were the spontaneous mutations identified. The mutation frequencies calculated by the inclusion of a mutant internal standard (MIS) in the RSM method, revealed that the non-coding intron 6 region and the exon 4 region had a 10-fold higher mutation frequency than the exon 5 region. This heterogenous distribution of mutations and their differential mutation frequencies, were probably a consequence of the greater selection in the coding regions in p53 function. However, the actual mechanism of differential mutation induction is, as yet, to be defined.

1,2-Dimethylhydrazine↗
PubMed1997

The detection of genotoxin-induced DNA adducts in the common mussel Mytilus edulis.

In order to establish the capacity of Mytilus spp. to form genotoxin-DNA adducts, a series of in vitro and in vivo studies were conducted in which tissue samples and animals were exposed to five model genotoxins. Following the in vitro characterization of the major adducts induced by the compounds, a series of in vivo studies were conducted to determine if the levels of genotoxin-DNA adduct formation followed a dose response. The results of these studies suggested that under appropriate conditions, DNA adducts in the hepatopancreas could be used as molecular dosimeters of exposure to genotoxic compounds in the species. However, these studies also revealed that the successful detection of such genotoxin-DNA adducts depends largely upon their chromatographic properties and thus the vigour of the characterization undertaken.

2-Acetylaminofluorene↗
PubMed1997

Do general practitioners inform patients of the association between Helicobactor pylori infection and gastric cancer prior to determining serostatus?

The availability of non-invasive tests for the detection of Helicobactor pylori infection in primary care is increasing. However, the World Health Organization (WHO) has recently labelled H. pylori as a Class 1 carcinogen. We describe how frequently general practitioners (GPs) inform patients of this association prior to offering an H. pylori serology test, and discuss the possible consequences of withholding this information.

Family Practice↗
PubMed1996

The detection and evaluation of aneugenic chemicals.

Although aneuploidy makes a significant contribution to both somatic and inherited disease the mechanisms by which environmental chemicals may induce numerical chromosome aberrations are only poorly defined. The European Union Project was aimed to further our understanding of those chemical interactions with the components of the mitotic and meiotic cell division cycle which may lead to aneuploidy and to characterise the parameters such as cellular metabolism which may influence the activity of aneugenic chemicals. C-mitosis can be induced by the highly lipophilic polychlorinated biphenyl and the completion of mitosis and cleavage can be modified by agents which deplete cellular levels of reduced glutathione. Modifications of the fidelity of chromosome segregation were produced by inhibiting the functioning of topoisomerase II during chromatid separation. In contrast, the modification of centromere integrity resulted in chromosome breakage as opposed to disturbance of segregation. Modifiers of tubulin assembly and centriolar functioning in somatic cells such as acrylamide, vinblastine and diazepam reproduced their activity in rodent bone marrow and male germ cells. The analysis of chromosome malsegregation in Aspergillus nidulans by a structurally related series of halogenated hydrocarbons was used to develop a QSAR model which had high predictive value for the results of fungal tests for previously untested related chemicals. Metabolic studies of potential aneugens in genetically engineered human lymphoblastoid cells demonstrated the detoxification of the aneugenic activity of chloral hydrate and the activation of 2,3-dichlorobutane, 1,1,2-trichloroethane and trichloroethylene by Phase I biotransforming enzymes. Cell transformation studies in Syrian hamster dermal cultures using a panel of 22 reference and or potential aneugens indicated that 15 of the 22 produced positive results following single exposures. Five of the aneugens which were negative following single exposures produced positive results where cultures were continuously exposed for up to 6 weeks to low concentrations following a single non-transforming exposure to the mutagen dimethyl sulphate. The transformation studies indicate that a significant proportion of chemical aneugens are potential complete carcinogens and/or co-carcinogens. To optimise the enumeration of chromosomes following exposure to potential chemical aneugens whole chromosome paints and centromere specific probes suitable for use in fluorescence in situ hybridisation (FISH) were developed for the rat, mouse and Chinese hamster and selected human probes evaluated for their suitability for routine use. Molecular chromosome probes were used to develop protocols for enumerating chromosomes in metaphase cells and centromeres and micronuclei in interphase cells. The analysis of segregation of specific centromeres in binucleate cells following cytochalasin B treatment was shown to be a potentially valuable system for characterising non-disjunction following chemical exposure. Whole chromosome paints and centromere specific probes were used to demonstrate the presence of dose-response thresholds following treatment with a reference panel of spindle inhibiting chemicals. These data indicate that the FISH technology is suitable for evaluating the relative hazards of low-dose exposures to aneugenic chemicals.

Aneuploidy↗
PubMed1996

Somatic recombination, gene amplification and cancer.

The principle objective of this research programme, to analyse chemical induction of somatic recombination and related endpoints, i.e., mobilization of transposing elements and gene amplification, has been approached by means of several assay systems. These have included Drosophila, Saccharomyces and mammalian cell cultures. 6.1. Screening assays for mitotic recombination. A large number of chemicals have been investigated in the three Drosophila assay systems employed--the multiple wing hair/flare wing spot system developed by Graf et al., 1984, the white-ivory system developed by Green et al., 1986 and the white/white+ eye spot assay developed by Vogel (Vogel and Nivard, 1993). Particularly the screening of 181 chemicals, covering a wide array of chemical classes, by the last mentioned assay has shown that measurement of somatic recombination in Drosophila constitutes a sensitive and efficient short-term test which shows a remarkably good correlation with the agent score of 83 short-term tests analysed by ICPEMC (Mendelsohn et al., 1992; Table 2) as well as the assay performance in international collaborative programmes measuring carcinogen/non-carcinogens (de Serres and Ashby, 1981; Ashby et al., 1985, 1988). Also the wing spot assay has gained wide international recognition as a similarly sensitive test. These two assay systems in Drosophila measure both intrachromosomal events and interchromosomal recombination. The white-ivory system on the other hand is based on the loss of a tandem duplication in the white locus, the mechanism of which is less known, but probably involves intrachromosomal recombination. The difference in the mechanism between this assay and the former two was indicated by the lack of response to methotrexate in the white-ivory assay, while this compound was strongly recombinogenic in both the wing spot and white/white+ assays. The use of different strains of Drosophila with the white/white+ assay demonstrated the importance of the background genotype for the outcome of the test. Up to a 60-fold variation was found between the different genotypes in the response to procarcinogens, evidently dependent on differences in the metabolic activation of procarcinogens. In 1989 Schiestl presented results on intrachromosomal recombination in the strain RS112 of Saccharomyces, which indicated a capability to detect a range of chemical carcinogens, which gave negative results in Ames Salmonella assay. Such a test system, which could identify a larger range of potential carcinogens than conventional short-term tests evidently would be of great value and it therefore seemed of importance to follow up the observations by Schiestl. However, studies within this programme on the same strain of Saccharomyces, as well as the strains D7 (measuring intragenic recombination, intergenic recombination, and point mutation) and JD1 (measuring intragenic recombination at two loci) could not support the observations and interpretation by Schiestl (1989). The Drosophila white-ivory system, which presumably responds primarily by intrachromosomal recombination, did not give positive results with these Salmonella-negative agents either. One system to measure mitotic recombination in mammalian cell cultures was developed in the present programme. It was based on heterozygous mutations in both alleles of the adenosine deaminase gene (ADA). The system selects for proficient recombinants generated by the deficient cells. So far only pilot experiments, indicating that this experimental system operates as planned, have been performed. 6.2 Mechanisms of mitotic recombination The induction of mosaic spots in the wing spot and the white/white+ assays is predominantly dependent on interchromosomal recombination. This is evident from the fact that heterozygous inversions reduce the frequency of spots. A relationship between the length of inversions and the reduction of spots was demonstrated in the white/white+ assay--the long inversion ln(l)sc4L

Animals↗
PubMed1996

Research on the mechanisms of action of aneugenic chemicals and regulatory approaches for their control in the European Communities.

The European Communities have developed a wide range of regulatory instruments for the control of chemical products sold and used within its geographical area. An important part of the testing requirements for most chemicals within the European Communities is the preparation of an information package on the potential mutogen properties of each chemical. Currently, no test requirements specify a unique test for aneugenic activity, although current methods such as in vitro cytogenetic and bone marrow micronucleus assays provide some useful indirect information on aneugenic activity. During the past 15 years the European Communities supported a series of collaborative research projects that have investigated the mechanisms by which chemicals induce aneuploidy and developmental studies of test methods for the detection of aneugenic chemicals. These projects led to the development of in vitro methods for the detection and quantification of induced nondisjunction and chromosome loss and the measurement of aneuploidy in rodent bone marrow. The European Communities projects have demonstrated the aneugenic potential of a diverse range of chemicals and their potential role in inherited disease and tumour induction. However, regulatory guidelines have yet to be modified to take advantage of the methods developed for the detection and evaluation of aneugenic chemicals.

Aneuploidy↗
PubMed1996

A study of the aneugenic activity of trichlorfon detected by centromere-specific probes in human lymphoblastoid cell lines.

The potential of the pesticide trichlorfon to induce mitotic aneuploidy has been investigated in genetically engineered human lymphoblastoid cell lines. Trichlorfon failed to induce micronuclei in the AHH-1 and MCL-5 cell lines when treated in media at normal cell culture pH (pH 7.3). Under a treatment pH of 5.5, trichlorfon exposures resulted in the induction of both chromosome loss and chromosome non-disjunction as measured by fluorescence in situ hybridisation (FISH) using a pan-centromeric probe for all human centromeres and centromere probes specific for chromosomes 2, 7 and 18. At treatment concentrations greater than 20 micrograms/ml trichlorfon also induced structural chromosome damage resulting in the production of centromere negative micronuclei.

Aneuploidy↗
PubMed1996

An investigation into the activation and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human cells.

We have investigated the induction of micronuclei by 15 chlorinated hydrocarbons in the cytochalasin B-blocked micronucleus assay utilizing genetically engineered cell lines. The human lymphoblastoid cell line AHH-1, with native cytochrome CYP1A1 activity, the MCL-5 cell line, which stably expresses cDNAs encoding human CYP1A2, 2A6, 3A4, 2E1 and microsomal epoxide hydrolase, and the h2E1 cell line, containing a cDNA for CYP2E1, were used in this study. We have demonstrated the induction of kinetochore-positive micronuclei by two chlorinated solvents, 2,3-dichlorobutane and 1,1, 2-trichloroethane, in the metabolically competent cell lines MCL-5 and h2E1. The MCL-5 and h2E1 cell lines have in addition shown the capacity to produce metabolites in the presence of methylene chloride, carbon tetrachloride, 1,2,3-trichloropropane, tetrachloroethylene, toluene and n-hexane, wich yield elevated micronucleus frequencies compared with the parental cell line AHH-1. Hexachloroethane failed to induce micronuclei in any of the cell lines and 1,2-dichloroethane and 1-chlorohexane induced micronuclei without the requirement for metabolic activation in all three cell lines. The MCL-5 cell line exhibited reduced micronucleus frequencies compared with the AHH-1 and h2E1 cell lines following exposure to 1,2-dichloroethylene, 1,3-dichloropropane, 1,1, 1-trichloroethane and 1,2,3-trichloropropane. The methodology used has shown the ability of metabolically competent cell lines expressing cDNAs encoding the cytochrome P450 isoenzymes to metabolize halogenated hydrocarbons to genotoxic species, including both clastogens and aneugens. The biotransformation of chemicals to aneugenic species has not previously been demonstrated.

B-Lymphocytes↗
PubMed1996

Mitotic non-disjunction as a mechanism for in vitro aneuploidy induction by X-rays in primary human cells.

A collaborative study of three laboratories compared the induction of aneuploidy by X-rays in human lymphocytes and fibroblasts. The induction of non-disjunction versus chromosome loss by X-rays was investigated using a variety of aneuploidy detection methods. Chromosome loss was determined by fluorescence in situ hybridization (FISH) with pan-centromeric probes in cytochalasin-B-blocked binucleated cells. Chromosome non-disjunction was estimated by FISH with chromosome-specific centromeric probes in binucleated interphase cells. Chromosomes were counted in parallel in lymphocyte metaphase cells; chromosome counts of the whole karyotype and counts of chromosomes 2 and 8 using chromosome paints. A major observation in spontaneous non-disjunction frequencies concerned the clear difference in frequencies observed between the two painted chromosomes in the same primary cells. When cells were irradiated elevated frequencies were observed for all the different cytogenetic endpoints. Although only a small number of the micronuclei were positive for the centromeric signal and presumably contained whole chromosomes, the absolute number %oC+ increased with dose. Higher rates of non-disjunction were found for irradiated cells; in fibroblasts a statistically significant increase was observed at a dose of 0.5 Gy. The detection of hyperdiploidy by means of chromosome counts and chromosome painting revealed an increase from doses of 1 Gy and higher. Comparison of the different methods detecting different endpoints indicates that non-disjunction may be an important mechanism leading to spontaneous and X-ray-induced aneuploidy. The relative radiosensitivity of aneuploidy induction was compared in two types of primary human cells - lymphocytes and fibroblasts. For chromosome loss both cell types showed similar results, whereas for non-disjunction fibroblasts seemed to be more sensitive. However, these differences may reflect a different sensitivity in the scoring methods used.

Aneuploidy↗
PubMed1996

A comparison of conventional metaphase analysis of Giemsa-stained chromosomes with multi-colour fluorescence in situ hybridization analysis to detect chromosome aberrations induced by daunomycin.

Chromosome aberrations induced by daunomycin, a widely used positive control compound for in vitro cytogenetics assays, were identified by multi-colour fluorescence in situ hybridization with probes for chromosomes 1, 2 and 3. The frequency and distribution of aberration types were compared to conventional metaphase analysis of Giemsastained chromosomes from parallel human lymphocyte cultures. Multi-colour chromosome painting was a more sensitive method for detecting daunomycin-induced chromosome aberrations compared with conventional metaphase analysis because: (i) a higher level of statistical significance was achieved at low doses; and (ii) the increases in aberration frequencies compared with controls were greater. The majority of exchanges identified by Giemsastaining were unstable and were likely to lead to cell death. In contrast, those detected by FISH were mostly stable exchanges which may be transmitted to cell progeny. Multicolour FISH using whole chromosome probes may provide an elegant solution to the problem of identifying non-lethal, heritable exchange events. The benefit of this technique is the quantification of a cytogenetic endpoint directly associated with carcinogenesis.

Adult↗