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U Graf

Publications and source records attributed to U Graf.

At least 19 recordsLinked to original sources
PubMed2005

Genotoxicity of neutrons in Drosophila melanogaster. Somatic mutation and recombination induced by reactor neutrons.

This paper describes the observation of a direct relationship between the absorbed doses of neutrons and the frequencies of somatic mutation and recombination using the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. This test was used for evaluating the biological effects induced by neutrons from the Triga Mark III reactor of Mexico. Two different reactor power levels were used, 300 and 1000 kW, and two absorbed doses were tested for each power level: 1.6 and 3.2 Gy for 300 kW and 0.84 and 1.7 Gy for 1000 kW. A linear relationship was observed between the absorbed dose and the somatic mutation and recombination frequencies. Furthermore, these frequencies were dependent on larval age: In 96-h-old larvae, the frequencies were increased considerably but the sizes of the spots were smaller than in 72-h-old larvae. The analysis of the balancer-heterozygous progeny showed a linear absorbed dose- response relationship, although the responses were clearly lower than found in the marker-trans-heterozygous flies. Approximately 65% of the genotoxicity observed is due to recombinational events. The results of the study indicate that thermal and fast neutrons are both mutagenic and recombinagenic in the D. melanogaster wing SMART, and that the frequencies are dependent on neutron dose, reactor power, and the age of the treated larvae.

Animals↗
PubMed2001

Mast cell activation in acquired chronic urticaria-angioedema.

Mast cells play a central role in the pathogenesis of many allergic disorders. They can be activated in different ways. The present study was focused to evaluate the role of mast cells in acquired chronic urticaria-angioedema induced by gastroesophageal reflux. Tryptase, an important marker of mast cell activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from acquired chronic urticaria-angioedema. Results were compared with the results of seven healthy control subjects. Moreover, data were compared with those of 13 subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results underline the central role of mast cells in the inflammation of acquired chronic urticaria-angioedema.

Adult↗
PubMed2001

Taxanes: the genetic toxicity of paclitaxel and docetaxel in somatic cells of Drosophila melanogaster.

In this study, the taxanes, paclitaxel and docetaxel were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. These relatively new drugs are used in cancer therapy and show great promise in the treatment of a variety of cancers. Their major cellular target is the alpha,beta-tubulin dimer but, unlike other spindle poisons, they stabilize microtubules by a shift towards assembly, producing nonfunctional microtubule bundles. The Drosophila wing Somatic Mutation and Recombination Test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the standard version of SMART (with normal bioactivation) and a variant version with increased cytochrome P450-dependent biotransformation capacity. In the standard assay, docetaxel was found to be aneuploidogenic; this was effectively abolished by a high cytochrome P450-dependent detoxification capacity. This suggests, as previously reported, the involvement of this family of enzymes in the detoxification of docetaxel rather than in its activation. In contrast, paclitaxel was clearly non-genotoxic at the same (millimolar) concentrations as used for docetaxel in both crosses. The weak responsiveness of SMART assays to aneugenic compounds, the weaker ligand and assembly action of paclitaxel and the more rapid reversibility of the microtubules formed with this compound, may have caused the negative response observed in the present study.

Angiogenesis Inhibitors↗
PubMed2001

Recombinagenic activity of four compounds in the standard and high bioactivation crosses of Drosophila melanogaster in the wing spot test.

The wing somatic mutation and recombination test (SMART) using Drosophila melanogaster was employed to determine the recombinagenic and mutagenic activity of four chemicals in an in vivo eukaryotic system. Two different crosses involving the wing cell markers mwh and flr(3) were used: the standard cross and a high bioactivation cross. The high bioactivation cross is characterized by a high constitutive level of cytochromes P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Three-day-old larvae derived from both crosses were treated chronically with the oxidizing agent potassium chromate and with the three procarcinogens cyclophosphamide, p-dimethylaminoazobenzene and 9,10-dimethylanthracene. From both crosses two types of progeny were obtained: marker-heterozygous and balancer-heterozygous. The wings of both genotypes were analysed for the occurrence of single and twin spots expressing the mwh and/or flr(3) mutant phenotypes. In the marker-heterozygous genotype the spots can be due either to mitotic recombination or to mutation. In contrast, in the balancer-heterozygous genotype only mutational events lead to spot formation, all recombination events being eliminated. The oxidizing agent potassium chromate was equally and highly genotoxic in both crosses. Surprisingly, the promutagen cyclophosphamide also showed equal genotoxicity in both crosses, whereas p-dimethylaminoazobenzene was negative in the standard cross, but clearly genotoxic in the high bioactivation cross. 9,10-Dimethylanthracene showed a rather weak genotoxicity in the high bioactivation cross. Analyses of the dose-response relationships for mwh clones recorded in the two wing genotypes demonstrated that all four compounds are recombinagenic. The fraction of all genotoxic events which are due to mitotic recombination ranged from 83% (9,10-dimethylanthracene) to 99% (p-dimethylaminoazobenzene). These results demonstrate that the wing spot test in Drosophila is most suited to the detection of recombinagenic activity of genotoxic chemicals.

Animals↗
PubMed2000

Interference of tannic acid on the genotoxicity of mitomycin C, methylmethanesulfonate, and nitrogen mustard in somatic cells of Drosophila melanogaster.

The modulating effects of tannic acid (TA) on somatic mutation and mitotic recombination induced by methylmethanesulfonate (MMS), nitrogen mustard (HN2), and mitomycin C (MMC) were evaluated in the standard (ST) cross of the wing spot test in Drosophila melanogaster using co- and posttreatment protocols. It was shown that TA alone did not modify the spontaneous frequencies of single and twin spots, which means that this polyphenol neither acts as a genotoxin nor exerts any antigenotoxic effect over spontaneous DNA lesions. However, the simultaneous administration of genotoxins with TA can lead to considerable alterations of the frequencies of induced wing spots in comparison to those with administration of the genotoxins alone. In fact, TA produced a significant increase in HN2-induced wing spots with enhancements between 90 and 160%. For MMS, the enhancement was 38% in the highest TA concentration tested. In contrast, a significant protective action of this polyphenol was observed in combined treatments with MMC (64 to 99% inhibition). Moreover, the data from TA posttreatments demonstrated that this agent is not effective in exerting protective or enhancing effects on the genotoxicity of MMS, HN2, or MMC. One feasible mechanism of TA action is its interaction with the enzyme systems catalyzing the metabolic detoxification of MMS and HN2, which may also be involved in the bioactivation of MMC.

Animals↗
PubMed1999

The synergistic effects of vanillin on recombination predominate over its antimutagenic action in relation to MMC-induced lesions in somatic cells of Drosophila melanogaster.

The wing Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster was used to study the modulating action of vanillin (VA) in combination with the alkylating agents mitomycin C (MMC), methylmethanesulphonate (MMS) and the bifunctional nitrogen mustard (HN2). Two types of treatments with VA and each of the three genotoxins were performed: chronic co-treatments of three-day-old larvae of the standard cross as well as post-treatments after acute exposure with the genotoxins. This allowed the study of the action of VA not only in the steps that precede the induction of DNA lesions but also in the repair processes. The overall findings from the co-treatment series suggest that ingestion of VA with MMS or MMC can lead to significant protection against genotoxicity; but this is not the case with HN2. Antioxidant activity, suppression of metabolic activation or interaction with the active groups of these two alkylating agents could be mechanisms by means of which VA exerts its desmutagenic action. In contrast, when evaluated in the post-treatment procedure, VA causes two antagonistic effects on the genotoxicity of MMC: (i) synergism on recombination (172.8%) and (ii) protection against mutation (79.0%). Consequently, both activities together lead to a considerable increase in mitotic recombination. In spite of being separate events, recombination and gene mutation are correlated during mitosis since the fate of a DNA lesion depends on the repair pathway followed. Our results may suggest that VA is a modifying factor that blocks the mutagenic pathway and consequently directs the MMC-induced lesions into a recombinational repair. Furthermore, VA did not modify the genotoxicity when administered after treatments with HN2 or MMS. Therefore, the major finding of the present study, namely the co-recombinagenic activity of VA on MMC-induced lesions, seems to be related to the type of induced lesion and consequently to the repair processes involved in its correction.

Animals↗
PubMed1999

Genotoxicity testing of six insecticides in two crosses of the Drosophila wing spot test.

Among the great variety of genotoxicity assays available, the wing spot test in Drosophila melanogaster has some characteristics that make it very suited for the screening of genotoxic activity, i.e., it is an easy and inexpensive assay using a eukaryotic organism in vivo. One of the most interesting characteristics of the assay is its capacity to detect genotoxic activity of promutagens without the necessity of an exogenous metabolic activation system. In this paper we present results obtained with a recently developed high bioactivation cross of the wing spot test (NORR cross). The positive results obtained with the five well-known procarcinogens 7, 12-dimethylbenz[a]anthracene, N-nitrosopyrrolidine, p-dimethylaminoazobenzene, diethylnitrosamine and urethane clearly show that the NORR strains are similar to the other high bioactivation strains previously described, but they lack their methodological disadvantages. We have tested six insecticides, which are characterised by having contradictory results in other genotoxicity tests, using both the standard and the high bioactivation (NORR) cross. The six insecticides analysed are the pyrethroid allethrin, the methylenedioxyphenolic compound piperonyl butoxide, the chlorinated hydrocarbons dieldrin and endrin, and the organophosphates dimethoate and malathion. We obtained negative results for all six compounds. Our results show the suitability of the wing spot test for the evaluation of compounds at the first level of genotoxicity testing.

Animals↗
PubMed1999

Genotoxicity of organic extracts of airborne particles in somatic cells of Drosophila melanogaster.

Complex mixtures extracted from air filters exposed for 24 h in two sessions (27 July and 02 August 1991) and at two locations (Merced, downtown, and Pedregal de San Angel, south-west) in Mexico City were analysed. The organic extracts were from airborne particles equal or smaller than 10 microns (PM10), and from total suspended particles (TSP). These organic extracts were assayed in the somatic mutation and recombination test (SMART) in wings of Drosophila melanogaster using two different crosses as well as in the Salmonella/microsome assay using strain TA98 with and without S9 fraction. The presence of polycyclic aromatic hydrocarbons (PAH) in the extracts was determined by gas chromatography. The genotoxic activities observed in the two test systems were comparable with the indirect mutagens producing greater response than the direct mutagens. The quantities of particulate matter as well as the genotoxic activities were higher on 02 August than on 27 July 1991 for both locations. The amounts of airborne particles and the resulting genotoxic activities were higher at Merced than at Pedregal. In both biological systems, PM10 were more genotoxic than TSP. These results demonstrate the sensitivity of the Drosophila wing SMART-which is an in vivo eukaryotic genotoxicity assay-as a biological monitor of environmental pollution related to airborne particles.

Air Pollutants↗
PubMed1999

Gastric asthma: an unrecognized disease with an unsuspected frequency.

Bronchial asthma is a disease that has been recognized for centuries, which is influenced mainly by genetic and environmental factors. The current interest of bronchial asthma is focused to ascertain the causes and the mechanisms that induce bronchoconstriction. Recently, abnormalities of the esophageal and gastric tracts have become important related areas for research. In predisposed individuals, these abnormalities can trigger or worsen the particular syndrome better known as "gastric asthma." In bronchial asthma the disorder of gastroesophageal reflux (GER) occurs more often than would be expected by chance. The neurogenic mechanism is considered to be the main cause of bronchoconstriction. The diagnosis of gastric asthma is particularly difficult and it should be considered also when GER is less evident or not recognized. In asthmatic patients the recognition of gastric abnormalities is very relevant for therapeutic problems also when GER is in a subclinical stage. In fact, many drugs used in the treatment of bronchial asthma can promote or enhance GER and subsequently they can worsen the symptoms of gastric asthma.

Asthma↗
PubMed1999

The results of assays in Drosophila as indicators of exposure to carcinogens.

Drosophila has fulfilled a dual function in the field of genetic toxicology: for use in short-term tests for identifying carcinogens and in a model for studies of the mechanisms of mutagenesis by chemicals. Until the mid-1980s, use of Drosophila in short-term tests was restricted to assays for genetic damage in germ cells, mostly in males. The largest database, on 700-750 chemicals, is available for the test for sex-linked recessive lethal (SLRL) forward mutation. The database for assays of the consequences of chromosomal breakage--reciprocal translocations and chromosome loss--is smaller, with about 100 chemicals tested. Comparative studies conducted within the US National Toxicology Program showed that SLRL is a better end-point than reciprocal translocation: of 66 chemicals (68 entries) that induced SLRL, only 28 (41%) induced reciprocal translocation. The major weakness of the SLRL assay is its low sensitivity (0.27-0.79) for mammalian genotoxins. A strength of the SLRL mutation test is its high specificity, which is close to 1. Thus, whereas a negative response in Drosophila provides little evidence for genotoxicity, a positive response (SLRL frequency > or = five times the control level) provides good evidence that a chemical is a trans-species mutagen and probably also carcinogenic to mammals. The poor performance of the SLRL test revealed in several collaborative studies led to the development of assays for recombination in somatic cells of Drosophila. Two of these tests have been evaluated for all known classes of genotoxic chemical: the mwh/flr wing spot test on more than 400 chemicals and the white/white+ eye spot test on about 220 chemicals. Of 24 carcinogens that gave negative or inconclusive test results in the SLRL assay, 22 gave positive results in one or both of the somatic systems. Their better performance in comparison with the germ-line assays is primarily the result of their low cost (5-10% of that needed for an SLRL assay), allowing use of multiple doses and protocols and the use of distinct tester strains with heterogeneity for activation of procarcinogens. For qualitative and quantitative studies on structure-activity and activity-activity relationship, only germ-line system have been used. In general, clear relationships between physico-chemical parameters (s values, O6/N7-alkylguanine ratios), carcinogenic potency in rodents and several descriptors of genotoxic activity in germ cells (from mice and Drosophila) became apparent when the following descriptors were used: (1) estimates of TD50 (lifetime doses expressed in milligrams per kilogram body weight or millimoles per kilogram body weight) from bioassays for cancer in rodents; (2) the degree of germ-cell specificity, i.e. the ability of a genotoxic agent to induce mutations at practically any stage of development of Drosophila and mouse spermatogenesis, as opposed to a more specific response in postmeiotic stages of both species; (3) the M(NER-)/M(NER+) hypermutability ratio, determined in a repair assay in Drosophila germ cells; (4) the ratio of chromosomal aberrations to SLRL in postmeiotic germ cells of Drosophila, i.e. the comparative efficiency of a carcinogen to induce these two end-points; (5) mutational spectra induced at single loci, i.e. the seven loci used in the specific-locus test in mice and the vermilion, white and rosy genes of Drosophila; and (6) the doubling doses in milligrams or millimoles per kilogram for specific locus induction in mice. On the basis of these parameters, alkylating agents were classified into three categories in terms of germ-cell specificity, which is primarily due to stage-related differences in DNA repair, clastogenic efficiency, type of mutation spectra and carcinogenic potency in rodents. The three categories allow predictions of the genotoxicity of alkylating agents but not yet for other categories of genotoxic carcinogens.

Animals↗
PubMed1998

Antigenotoxicity studies in Drosophila melanogaster.

The fruit fly Drosophila melangaster with its well developed array of genotoxicity test systems has been used in a number of studies on antigenotoxicity of various compounds and mixtures. In recent years, the newly developed Somatic Mutation and Recombination Tests (SMART) have mainly been employed. These one-generation tests make use of the wing or eye imaginal disc cells in larvae and have proven to be very efficient and sensitive. They are based on the principle that the loss of heterozygosity of suitable recessive markers can lead to the formation of mutant clones of cells that are then expressed as spots on the wings or eyes of the adult flies. We have employed the wing spot test with the two markers multiple wing hairs (mwh,3-0.3) and flare (flr,3-38.8). Three-day-old larvae, trans-heterozygous for these markers, are treated chronically or acutely by oral administration with the test compound(s) or complex mixtures. For antigenotoxicity studies, chronic co-treatments can be used, as well as separate pre-treatments with an antigenotoxic agent followed by a chronic treatment with a genotoxin. After eclosion, the wings of the adult flies are scored for the presence of single and twin spots. These spots can be due to different genotoxic events: either mitotic recombination or mutation (deletion, point mutation, specific types of translocation, etc.). The analysis of two different genotypes (one with structurally normal chromosomes, one with a multiply inverted balancer chromosome) allows for a quantitative determination of the recombinagenic activity of genotoxins. Results of two separate studies presented: (1) instant coffee has antirecombinagenic but not antimutagenic activity in the wing spot test; and (2) ascorbic acid and catechin are able to protect against in vivo nitrosation products of methyl urea in combination with sodium nitrite.

Animals↗
PubMed1998

Analysis of the in vivo nitrosation capacity of the larvae used in the wing somatic mutation and recombination test of Drosophila melanogaster.

The in vivo nitrosation capacity of third-instar larvae of Drosophila melanogaster was assessed using the wing somatic mutation and recombination test (SMART). Larvate derived from two different crosses, the standard cross (ST) and the high bioactivation cross (HB) both involving the recessive wing cell markers multiple wing hairs (mwh) and flare (flr3), were used. The HB cross is characterised by an increased cytochrome P450-dependent bioactivation capacity for promutagens and procarcinogens. The larvae were treated either with methyl urea, sodium nitrite or its combination. N-Nitrosomethylurea was used as a positive control. The wings of the resulting flies were analysed for the occurrence of mutant spots produced by various types of mutational events or by mitotic recombination. Methyl urea is negative in the ST and the HB cross, whereas sodium nitrite is weakly genotoxic in both crosses. However, the combination of both compounds produces highly increased frequencies of mutations and recombinations predominantly in the HB cross. The genotoxic effects produced by the combined treatments were considerably increased when mashed potatoes or an agar-yeast medium were used for the treatment instead of the standard instant medium. Treatment of larvae with the mixture resulting from the in vitro reaction of nitrosation precursors also resulted in high frequencies of induced spots comparable to those recorded with the potent genotoxin N-nitrosomethylurea. Further experiments showed that the genotoxic effect resulting from the in vivo exposure to nitrosation precursors can be reduced by co-treatment with catechin, a known nitrosation inhibitor. The present study demonstrates that the wing spot test is well suited for the determination of genotoxicity produced by in vivo nitrosation processes and for the study of their modulation by individual compounds or dietary complex mixtures.

Animals↗
PubMed1997

Recombinagenic activity of integerrimine, a pyrrolizidine alkaloid from Senecio brasiliensis, in somatic cells of Drosophila melanogaster.

Integerrimine (ITR), a pyrrolizidine alkaloid from Senecio brasiliensis, was tested for genotoxicity using the wing somatic mutation and recombination test (SMART) in Drosophila melanogaster. The compound was administered by chronic feeding (48 hours) of 3-day-old larvae. Two different crosses involving the markers flare (flr) and multiple wing hairs (mwh) were used, that is, the standard (ST) cross and the high bioactivation (HB) cross, which has a high cytochrome P450-dependent bioactivation capacity. In both crosses, the wings of two types of progeny were analyzed, that is, inversion-free marker heterozygotes and balancer heterozygotes carrying multiple inversions. ITR was found to be equally potent in inducing spots in a dose-related manner in the marker heterozygotes of both crosses. This indicates that the bioactivation capacity present in larvae of the ST cross is sufficient to reveal the genotoxic activity of ITR. In the balancer heterozygotes of both crosses, where all recombinational events are eliminated due to the inversions, the frequencies of induced spots were considerably reduced which documents the recombinagenic activity of ITR. Linear regression analysis of the dose response relationships for both genotypes shows that 85% to 90% of the wing spots are due to mitotic recombination.

Animals↗
PubMed1997

[Peritonitis in horses: a retrospective study of 95 cases].

Clinical signs of horses with peritonitis were colic (67.4%), elevated heart rate (53.2%), altered mucous membranes (75.8%), reduced intestinal motility (63.2%), increased tension of the abdominal wall (69.9%) and pyrexia (45.1%). The amount of obtained peritoneal fluid was increased in 62.3% of the horses. Colour and translucency of the peritoneal fluid were abnormal in 98.8% of the patients. The nucleated cell count was 83.5 (10-595) x 10(3)/microliter, protein content 35.6 g/l (+/-14.2), specific gravity 1027.3 (+/-7.4) and the relative amount of neutrophils was 87.8% (+/-11). The physical examination and the examination of the peritoneal fluid were of diagnostic value. Complete blood count and blood chemistry indicated the degree of circulatory depression and the duration of the disease. Overall mortality was 47.4% (45/95). Non-survivors had significantly more often an increased heart- and respiratory rate, altered mucous membranes, an increased tension of the abdominal wall, reduced intestinal motility and increased amount of peritoneal fluid. Packed cell volume, urea, creatinine, glutamatdehydrogenase, sorbitoldehydrogenase, lactatdehydrogenase and blood pH were significantly different between survivors and non-survivors. All these parameters were statistically of no prognostic value.

Animals↗
PubMed1996

Analysis of mitotic recombination induced by several mono- and bifunctional alkylating agents in the Drosophila wing-spot test.

Mitotic recombination induced by six alkylating agents has been studied in the wing-spot test of Drosophila melanogaster. The model mutagens chosen have different models of action at the DNA level. These are: the direct-acting small alkylating agent methylmethanesulfonate (MMS), the small promutagens N-dimethylnitrosamine (DMN) and N-diethylnitrosamine (DEN), the bifunctional cross-linking alkylating agents mitomycin C (MMC), chlorambucil (CLA) and monocrotaline (MCT). Flies of the standard cross (flr3 / TM3, Bds females and mwh males) were used to produce the larvae to be treated. Three-day old Drosophila larvae were exposed by chronic feeding for 48 h to three different concentrations of all six alkylating agents. Acute feeding for only 2 h was used in addition with DEN and MMC. Wings of the marker-heterozygous (mwh+ / + flr3) as well as of the balancer-heterozygous (mwh+ / TM3, Bds) progeny were analysed. The ranking of the compounds with respect to their genotoxic potency, based on mwh clone formation frequency in marker-heterozygous wings was: MMS > MNC > DMN > CLA approximately MCT > DEN. The ranking with respect to the induction of twin spots, which are produced by mitotic recombination exclusively, was: MMS > DMN > MMC > MCT > CLA > DEN. The quantitative determination of recombinagenic activity, based on mwh clone formation frequencies obtained in both types of wings, gave the following values: MMS, 93%; MCT, 87%; CLA, 80%; MMC, 73%; DMN, 67%; DEN, 22%. A clear relationship exists between the extent of N-alkylation of DNA and the efficiency of the monofunctional agents MMS and DMN as well of the bifunctional agents MCT, CLA and MMC to induce mitotic recombination. This contrasts with the ethylation of base oxygen atoms and the resulting lower efficiency of DEN to produce mitotic recombination.

Alkylating Agents↗
PubMed1996

The somatic white-ivory eye spot test does not detect the same spectrum of genotoxic events as the wing somatic mutation and recombination test in Drosophila melanogaster.

A groups of six chemical compounds was tested in parallel in two different somatic genotoxicity assays in Drosophila melanogaster, the wing somatic mutation and recombination test (SMART) and the white-ivory eye spot test. The wing spot test makes use of the wing cell markers multiple wing hairs (mwh) and flare (flr) and detects both mitotic recombination and various types of mutational events. The white-ivory eye spot test makes use of the white-ivory (wi) quadruplication and detects the somatic reversion of the recessive eye color mutation wi to the wild-type (w+). Three- or two-day-old larvae were fed chronically with the compounds ethylnitrosourea (ENU), N-nitrosopyrrolidine (NNP), caffeine (CAF), chromium (VI) oxide (CRO), potassium chromate (POC), and 2,4-dichlorophenoxyacetic acid (2,4-D). All six compounds are genotoxic to various degrees in the wing spot test. The percentage of the genotoxic activity that is due to mitotic recombination was between 84% and 91% for the hexavalent chromium compounds CRO and POC and about 68% for 2,4-D. In contrast, ENU and NNP showed only 46% and 25% recombinagenic activity, respectively. In the white-ivory eye spot test, the three compounds (CRO, POC, and 2,4-D) with high recombinagenic activity and CAF were clearly nongenotoxic, whereas only ENU and NNP gave a positive response. From these results, it is concluded that the spectrum of genotoxic events detected by the two assays is different. In particular, the white-ivory eye spot test appears not to detect mitotic recombination the way the wing spot test does.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1996

Protection by coffee against somatic genotoxicity in Drosophila: role of bioactivation capacity.

The protective effects of coffee against somatic mutation and mitotic recombination induced by cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE) were evaluated in the standard (ST) and high bioactivation (HB) crosses of the wing spot test in Drosophila melanogaster. These two crosses are characterized by different constitutive levels of cytochrome )-450-dependent enzyme activities. 3-day old larvae transheterozygous for the wing cell markers mwh (multiple wing hairs) and flr3 (flare3) were fed until pupation on medium containing a genotoxin alone or its combination with different concentrations of instant coffee. subsequently, the wings of the resulting adult flies were analysed for detecting single spots (mwh or flr3) originating from mutational or recombinational events as well as twin spots (mwh and flr3) originating exclusively from recombination. The results showed high sensitivity of the HB cross to URE. Co-administration of instant coffee was effective in exerting significant dose-related inhibitory effects on the genotoxicity of URE in the ST and the genetically susceptible HB cross. Similarly, coffee showed significant dose-related inhibitory effects on the genotoxicity of MMC in both crosses. The same protective effect was also observed with one concentration of coffee in combination with CPH. Pretreatment of 2-day-old HB larvae with coffee for 24 hr followed by treatment with URE was also effective in significantly reducing the induction of mutation and recombination. The magnitude of the protective effects of coffee against these three genotoxins was independent of the genotype of the larvae used for treatment, that is it was independent of the bioactivation capacity of these larvae. The study demonstrates the suitability of this assay for obtaining qualitative and quantitative data on the result of interactions among a genotoxin, an inhibitor of genotoxicity and bioactivation capacity of the host.

Animals↗