Induction of tumor clones in D. melanogaster wts/+ heterozygotes with chemical carcinogens.

Ten chemicals were assessed for blastomogenic activity in adult wts/+ heterozygotes of D. melanogaster. All of the strong mammalian carcinogens tested (benzo(a)pyrene (B(a)P), pyrene, aflatoxin B(1), 2-acetylaminofluorene (2-AAF) and cis-dichlorodihydroxydiamminoplatinum IV) were also shown to be strong Drosophila blastomogens. They induced several times more tumors than their counterparts that are less carcinogenic for mammals (4-acetylaminofluorene (4-AAF), aflatoxins B(2) and G(2)) and 4-(methylnitrosamino)-1-(-3-pyridine)-1-butanone (NNK). Benzo(e)pyrene (B(e)P) and pyrene demonstrated minor effects. Most tumors were localized on the wing and notum, which are the derivatives of the wing disc. Humeri derived from dorsal prothoracic disc and the abdominal tergites and sternites had the lowest number of tumors. The tumor frequency in the cross of the wild type females with wts(P2)/TM6B males was different from that in the reciprocal cross. The former type of cross exhibited consistently higher tumor frequency both in the experimental and control series.

[A statistical study of the growth and morphogenesis of axillary apparatus and notum in the Pth mutants of Drosophila]. / O nekotorykh statisticheskikh aspektakh rosta i morfogeneza struktur aksilliarnogo apparata i notuma drozofily (po rezul'tatam analiza mutantov Pth).

The regularities of morphogenesis of the ventral wing-hinge structures in the Pth mutants of Drosophila melanogaster were studied using statistical methods. Our views on the vectorial growth of presumptive wing hinge as an entire unity were independently confirmed using statistical methods. The expected duplication forms, the possibility of their one-dimensional classification, the expected number of possible types, and other aspects of duplication were discussed in view of other possible suggestions on the growth of the ventral wing hinge. The growth of the anterior half of the pteropleurum was shown to have a rigid organization, because it can be described as a function of one variable. The growth was shown to be exponential. The empirical formula that fits experimental data with a significance of 99.99% was chosen. The relationship between the presumptive ventral wing hinge and the presumptive notum in respect of growth was shown to be statistical (the coefficient of correlation r = 0.37) rather than functional. Therefore, such a morphologically united formation as the wing imaginal disk does not have a unified growth pattern. The growth pattern is composed from the individual growth patterns of its constituents that have a certain degree of independence.

[Duplications of the wing-hinge structures in the Pth mutants of drosophila melanogaster]. / Duplikatsii struktur krylovogo sharnira u mutantov Pth Drosophila melanogaster.

The Pth mutation of Drosophila melanogaster, a unique dominant mutation obtained by us, causes the notum duplications that are followed by the duplications of ventral and dorsal wing-hinge structures. The duplications of the wing hinge have a strictly coordinated structure, can be ranged in a continuous series, and are divided into four distinct types, none of which overlaps with the other. The order of the emergence of the ventral wing-hinge structures was determined in duplication forms, and the shape, size, and location of these structures were compared with normal parameters. The growth of the presumptive wing-hinge region was shown to have a vectorial mode; the directions of the main vectors and their center were determined. A geometrical model is proposed, which adequately explains the strict specificity in the structure of duplications as well as the agreement between the duplication forms to one another in each of the four types.

[Absence of mutagenic and carcinogenic properties in Mildronate]. / Otsutstvie mutagennykh i kantserogennykh svoistv u Mildronata.

Mutagenic and carcinogenic properties of mildronate (3-[2.2.2.-trimethyl hydrazonium]-propionate) have been studied for its marked immuno-stimulating and anti-ischemic action. When dosage up to 1,000 mg/dish was used no reversal of base-pair substitution or frame shift in S.typhimurium was observed. In drosophila females treated with mildronate, mosaic patches were, on the average, as frequent as in control. Although chronic treatment of female mice B6D2F1, C3H and SHR with mildronate was not followed by any change in tumor incidence, mammary gland adenocarcinoma development was slightly inhibited in mice C3H and SHR. The latter effect was in correlation with the antigonadotropic one of the drug and was not determined by its estrogenous properties. This pointed to the absence of mutagenic and carcinogenic properties which was confirmed in two short-term and one chronic experiments on mice of the three lines.

A Drosophila simulans mutant strain sensitive to benzo[a]pyrene and 2-acetylaminofluorene.

We have identified a Drosophila simulans mutant, 364 yu, that is sensitive to the toxic effects of the procarcinogens B(a)P and 2-AAF. Heterozygotes obtained by crossing it to the wild resistant Turku strain (female 364 yu x male Turku) were more sensitive than heterozygotes obtained from the reciprocal cross (female Turku x male 364 yu) to both the toxic and the mutagenic effects of B(a)P in Drosophila tests that measured lethality and the induction of somatic mosaicism, respectively. The non-carcinogens pyrene, B(e)P and 4-AAF were only weakly toxic and non-mutagenic. In the Ames test B(a)P activation with S15 fractions prepared from the homogenates of Drosophila larvae and imagoes of the 364 yu strain, as well as of the more resistant D. melanogaster y ++/+ w sn3 heterozygotes, did not significantly increase the number of S. typhimurium TA100 revertants even following pretreatment with inducers of microsomal monooxygenases (B(a)P, PCB, PB). As for 2-AAF, a certain increase was observed following only PB, but not B(a)P pretreatment. Possible mechanisms of B(a)P and 2-AAF sensitivity of the 364 yu strain, and perspectives on using it for monitoring genotoxic environmental pollutants, are discussed.

[Benzo(a)pyrene pretreatment of Drosophila simulans mutant strain results in the induction of aberrant isoform of cytochrome P-450 with increased capacity to metabolize benzo(a)pyrene]. / Predobrabotka benz(a)pirenom mutantnoi linii Drosophila simulans privodit k induktsii abberrantnoi izoformy tsitokhroma P-450 s povyshennoi sposobnost'iu metabolizirovat' benz(a)piren.

The basal level of benzo(a)pyrene monooxygenase, epoxide hydrolase and glutathione S-transferase activity as well as the content of cytochrome P-450 were found the same in both compared benzo(a)pyrene (BP) sensitive D. simulans strain 364yv and BP-resistant wild one (Turku). Phenobarbital pretreatment resulted in the same increase level of these enzyme activities in both strains. BP-pretreatment of 364yv flies decreased the amount of the cytochrome P-450 but raised up the turnover of BP per molecule of cytochrome P-450. SDS-polyacrylamide gel electrophoresis of the microsomal proteins from BP-pretreated 364yv flies (but not from Turku) showed an increased hemoprotein content in the 56000 band. The relationship between BP-sensitivity of the strain 364yv and BP-induced aberrant isoform of the cytochrome P-450 has been discussed.

[A mutant strain of Drosophila simulans sensitive to the toxic and mutagenic action of benz(a)pyrene]. / Mutantnaia liniia Drosophila simulans, chuvstvitel'naia k toksicheskomu i mutagennomu deistviiu benz(a)pirena.

A 364 yv strain sensitive to the toxic effect of benzo(a)pyrene (BP) was identified among 49 mutant strains of Drosophila simulans. Heterozygotes female 364 x male Turku obtained by crossing 364 yv species with those of wild BP-resistant Turku strain were more sensitive than female Turku x male 364 heterozygotes to both toxic and mutagenic effects of the carcinogen in the test of induction of somatic mosaicism with the yellow marker. Non-carcinogenic pyrene appeared weekly toxic and non-mutagenic. Possible mechanisms of 364 yv strain sensitivity to BP as well as vistas in application of the strain for monitoring genotoxic environmental pollution are discussed.

Mycotoxin induction of somatic mosaicism in Drosophila and DNA repair in mammalian liver cell cultures.

The genotoxic activity of four mycotoxins has been studied. A high level of somatic mutagenesis in imaginal disk of Drosophila melanogaster larvae and DNA repair synthesis in human embryo and adult rat liver cells cultures was induced only by the strong carcinogen aflatoxin B1. Patulin somewhat elevated the level of somatic mutations in D. melanogaster, but did not elicit DNA repair synthesis. Citrinin and stachybotryotoxin were inactive in both systems.

[Induction by mycotoxins of somatic mosaicism in Drosophila and DNA repair in mammalian liver cell cultures]. / Induktsiia mikotoksinami somaticheskogo mozaitsizma u drozofily i reparatsii DNK v kul'turakh kletok pecheni mlekopitaiushchikh.

The genotoxic activity of four mycotoxins has been studied. High level of somatic mutagenesis in imaginal discs of Drosophila melanogaster larvae and DNA repair synthesis in human embryo and adult rat liver cell cultures were inducible only by highly carcinogenic aflatoxin B1. Patulin, a weak direct-action carcinogenic substance, slightly elevated the mutagenesis in somatic cells of Drosophila but did not induce DNA repair synthesis in liver cell cultures. Citrinin that did not exhibit any carcinogenic properties when used alone and stachybotrotoxin with non-reported carcinogenic activity appeared inactive in the test-systems applied. The possibilities of rapid recognition of carcinogenic mycotoxins by detecting their genotoxic properties are discussed.

[Role of propionic acid, yeasts and ethyl alcohol in regulating the activity of H-factor in Drosophila simulans]. / O roli propionovoi kisloty, drozhzhei i étilovogo spirta v reguliatsii aktivnosti H-faktora u Drosophila simulans.

Effects of yeast, propionic acid and ethanol on the activity of H-factor, which sharply increases the frequency of somatic recombination in X-chromosomes of dorsal prothoracal disc cells in Drosophila simulans are studied. The frequency of yellow and singed mosaic spots in heterozygous yw ++/++sn1vHD. melanogaster females, inherited H-factor from the father (the stock sn1v) is estimated. The results of the varience analysis have shown that yeast and propionic acid regulate the activity of H-factor in cells of dorsal prothoracal disc, the interaction of yeast and propionic acid being also observed. Yeasts (or some unknown product of their metabolism) are the activator of H-factor; thus, when larvae eat much yeast, the frequency of yellow and singed mosaic spots in humeral region becomes high. A decrease of mosaic spot frequency under the increase of propionic acid content in nutrition medium is a result of the inhibitory effect of propionic acid on the yeast growth, but not of the direct repression of H-factor activity. So, propionic acid may be considered as a regulator of the second order. Ethanol does not activate H-factor. Changes in the content of yeast and propionic acid in nutrition medium do not affect the frequency of yellow and singed mosaic spots in other regions of D. simulans body, except humeral.

[An experimental study of the morphogenetic properties of several phenols inducing phenocopies of vitiligo]. / Eksperimental'noe issledovanie morfogennykh svoistv nekotorykh fenolov, indutsiruiushchikh fenokopiiu vitiligo

In an experiment with black guinea pigs a phenocopy of vitiligo was obtained by means of the exposure of the skin to the action of p-tert-butyl-phenol (PTBP) or to catechol (C). Two other compounds: 2,2-dihydroxy-diphenylpropane (DDP) and 2, 4, 6-tri-tert-butyl-phenol (TTBP) exerted a hypopigmentary effect. PTBP and C depigmented the skin but caused no preceding inflammation. Spots of depigmented (white) skin and hairs were surrounded by a zone of hyperpigmentation. Leukoderma proved to be stable, in some cases irreversible, and exhibited a tendency to progressing and spontaneous dissemination. In the experiments with Drosophila melanogaster both PTBP and C were observed to possess a morphogenetic capacity: they induced a change in the puparium colour (C), as well as of the colour of body and wings of adult flies, inducing also disturbances of wing development practically in 100% of individuals to which these substances were administrated with food at the larval stage. None of the four preparations tested exerted any mutagenic effect in cells of imaginal buds of Drosophila melanogaster.