[Nonrandom karyotype changes in chemically induced tumors of the Djungarian hamster]. / Nesluchainye izmeneniia kariotipa v khimicheski indutsirovannykh opukholiakh dzhungarskogo khomiachka.

In the cells of tumors induced with methylcholanthrene in wild type and mutant (pink-eyed dilution) Djungarian hamsters non-random involvement in structural changes of certain chromosomes (Xp, 3p and 3q, 7q, 8q) was revealed. In addition, characteristic feature of the majority of tumors was varied number of double-minutes chromosomes (DMs). In some tumors, the markers with long homogeneously or differentially stained regions (HSRs and DSRs) were also present. The DMs, HSRs and DSRs are known as the structures containing amplified genes.

[Nonrandom karyotype changes in human retinoblastomas]. / Nesluchainye izmeneniia kariotipa v retinoblastomakh cheloveka.

Cytogenetic analysis of 15 retinoblastomas developed in children having no constitutional chromosome 13 deletion has been carried out. In tumor cells, no deletion or loss of chromosome 13 was revealed. The specific marker chromosome i(6p) described in our previous publications has been found in 9 tumors. Besides, in two cases, trisomy of short arm of chromosome 6 was present. Other non-random changes (trisomy 1q, monosomy 16 and loss of one of the sex chromosomes) were not specific for retinoblastomas, because they were described in literature for some other tumors as well. The possible significance for genesis of retinoblastomas of dose multiplication of the genes located in the 6p is discussed.

[Sensitivity of grey and beige Djungarian hamsters to the blastomogenic action of 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene]. / Chuvstvitel'nost' serykh i bezhevykh dzhungarskikh khomiachkov k blastomogennomu deistviiu 7,12-dimetilbenz(a)antratsena i 3-metilkholantrena.

Sensitivity of normal gray and mutant beige (pink-eyed dilution mutation) Djungarian hamsters to the carcinogenic activity of 7,12-dimethylbenz (a) anthracene (DMBA) and 3-methylcholanthrene (MC) was studied. No differences between these two groups of animals which were given pills with DMBA were revealed. At the same time the beige females were found to be more sensitive to MC than males and hamsters of wild (gray) colour. Among tumours induced both by DMBA and MC fibrosarcomas prevailed both in the gray and beige hamsters. Fibrous histiocytomas were detected only in the MC-infected hamsters. Epithelial tumours were found only in females.

[Genetics of nephroblastoma. II. The incidence of developmental defects and dysplastic and asymmetrical traits in children with nephroblastoma]. / Genetika nefroblastomy. Soobshchenie II. Chastota porokov razvitiia, priznakov displastichnosti i asimmetrii u detei s nefroblastomoi.

The frequency of developmental defects and displasticity characters in children with nephroblastoma was determined in two groups--with early, up to 2 years manifestation of the tumor (ENB), in 40 patients, and with advanced nephroblastoma (ANB), in 59 patients (manifestation of the disease after 2 years). The data were correlated with control groups adequate for age (130 children). The frequency of serious developmental defects was higher in ANB group (20%) than in ENB group (7%). Over a half of developmental defects were hemihypertrophy and doubling of organs. One case of a child with the combination of nephroblastoma and Smith-Lemli-Opitz syndrome was defined. In ANB group an increased frequency of asymmetry in the conjugate organs (foot, hand, middle finger, ears) was found. Its direction is correlated with tumor localization (tumor site). In ENB group no analogous effect was shown. The data obtained present phenotype characteristics of groups with early and late manifestation of the disease which are probably different in their genesis and thus, their identification is necessary for the adequate medicogenetic consultation (examination).

[Gene mutation induction by the antitumor preparation ftorafur]. / Induktsiia gennykh mutatsii protivoopukholevym preparatom ftorafurom.

The influence of antitumor drug ftorafur (Ft) on the frequency of gene mutations to 8-azaguanine resistance was investigated. Asynchronous and synchronized cultures of SV40 transformed Djungarian hamster cells were used. The 2 to 3,5 fold increase in the frequency of gene mutations over the control level was observed after the Ft treatment. The most pronounced effect was obtained in the experiments with synchronized cultures, when exposed to Ft in the S-phase of the cell cycle.

[Chromosome disorders in retinoblastoma cells]. / Khromosomnye narusheniia v kletkakh retinoblastomy.

The karyotype of 7 unilateral retinoblastomas was studied. Loss or a gain of chromosomes and structural chromosomal changes were observed in all tumors. Modal chromosome number was pseudodiploid in four and near-diploid in three tumors. There were no sex chromosomes (X or Y) in 3 tumors. Four tumors were characterized by the presence of an identical marker chromosome--i(6p). Two other markers--lp+ and 17q+ (probably, not quite identical)--were present in 4 and 3 tumors, respectively. The cells of two retinoblastomas contained both i (6p) and 17q+ markers.

[Genetics of nephroblastoma. I. The heterogeneity of nephroblastoma]. / Genetika nefroblastomy. Soobshchenie I. Geterogennost' nefroblastomy.

The age of disease onset, sex, birth weight and stature were analysed in 150 children suffering from nephroblastoma. The material was compared with its own control group (92 normal children of the same age) and with the population data from literature. All nephroblastoma patients were divided into 2 groups by the age of disease onset: before 2 years old and after this. The proband birth weight and stature in the first group statistically differed from control and population exponents. Genetic heterogeneity of nephroblastoma is discussed.

[Relation of mammalian cell resistance to actinomycin D with a change in the karyotype and a decrease in cytoplasmic membrane permeability]. / Sviaz' rezistentnosti kletok mlekopitaiushchikh k aktinomitsinu D s izmeneniem kariotipa i umen' sheniem pronitsaemosti tsitoplazmaticheskoi membrany.

Djungarian hamster cell lines, selected for resistance to 2 microgram/ml of actinomycin D (AD) have been studied. These lines are 1000-4000 times more resistant to AD than the parent cells. AD-resistance is an unstable property. It is lost or diminished when the cells are grown in the absence of AD. The resistant cells show markedly reduced uptake of AD and unrelated agent - colchicin, which indicated that resistance to AD is due to the decrease of plasma membrane permeability. The chromosomal analysis of resistant lines revealed a specific abnormality in their kariotypes, namely, chromosomes containing "homogeneously staining regions" (HSR). These data support the suggestion that AD-resistance is associated with gene amplification.

[New developments in cancer cytogenetics]. / Novoe v tsitogenetike raka.

Three topics are discussed in the review: 1) The non-random and specific chromosome changes in human and animal tumors, 2) prezygotic chromosomal mutations which specifically predispose to some human tumors, and 3) the role of cytogenetics in the discovery and study of a novel phenomenon for mammalian cells-gene amplification which was revealed in a number of tumors and in cell lines resistant to some anticancer drugs.

[Somatic hybrids of normal and tumor Djzungarian hamster cells. I. Preferential elimination of chromosomes of the normal partner]. / Somaticheskie gibridy opukholevykh i normal'nykh kletok dzhungarskogo khomiachka. Soobshchenie I. Preimushchestvennaia utrata khromosom normal'nogo partnera.

Normal Djungarian hamster lymphoid cells were fused with SV40 transformed malignant fibroblasts. The resulting 11 hybrid clones were subjected to the chromosome analysis. The karyotype of hybrids proved to be unstable. In some cases the total tetraploid number of chromosomes in hybrids drastically decreased up to the near-diploid level close to that of the malignant parent cells. The G-band chromosome analysis showed that as a rule morphologically unchanged chromosomes were preferentially lost from the hybrid cells, the markers of the malignant partner being retained. On the basis of these data it is assumed than the hybrids between normal and tumour cells of Djungarian hamster preferentially lose the chromosomes of the normal parent cells during cultivation in vitro.

[Somatic hybrids of normal and tumor Djzungarian hamster cells. II. Manifestation of malignancy and karyotype features of hybrid tumors]. / Somaticheskie gibridy opukholevykh i normal'nykh kletok dzhungarskogo khomiachka. Soobshchenie II. Proiavlenie zlokachestvennosti i osobennosti kariotipa gibridnykh opukholei.

The hybrid clones derived from the fusion of tumour and normal cells of Djungarian hamster were tested for their ability to grow progressively in vivo and to form colonies in semisolid medium. In all cases the hybrids were able to produce tumours in animals, but tumorigenicity of different clones varied. Some clones had high take incidence of tumours comparable to that of malignant partner, others had a very low one. The hybrid clones differed in their ability to form colonies in soft agar. No correlation was found between the malignancy of the hybrid clones in vivo and their ability to grow in semisolid medium. Chromosome analysis of 23 hybrid tumours arising from the injections of the hybrid cells showed that in 18 tumours the drastic reduction of chromosomes from tetraploid to near-diploid level, comparable to that of malignant parent, took place. As a rule, morphologically unchanged chromosomes were preferentially lost from the hybrid tumour cells, the markers of the malignant partner being retained. Some hybrid tumours showed insignificant chromosome elimination of all pairs, except chromosomes of the IV and VIII pairs, their number always being reduced.

[Action of ftorafur on the chromosomes of normal and tumorous cells of the Djzungarian hamster in vitro]. / Deistvie ftorafura na khromosomy normal'nykh i opukholevykh kletok dzhungarskogo khomiachka in vitro.

The chromosome-breaking effect of antitumor agent ftorafur (0,1 mg/ml) was studied on cell cultures of normal and transformed Djungarian hamster's fibroblasts. After 24 hours of exposition with the drug 79% of aberrant malignant cells was registered, while the chromosomes of normal cells remained undamaged. After ftorafur's action for 2--12 hours and the following removal of the agent the level of aberrant metaphase among normal cells rose to 11--15%. Chromatid breaks were the predominant type of drug-induced aberrations. Thse results confirm the idea that ftorafur blocks the cell cycle of normal fibroblasts and that it's necessary to wash the drug off some period before fuxation in order to reveal its chromosome-breaking effect in metaphase cells. The striking distinctions in susceptibility of normal and malignant cells to the mutagenic effect of ftorafur is partly due to the distrubances of the cell cycle caused by this drug.

[Mechanism of the chromosome damaging effect of ftorafur]. / Izuchenie mekhanizma povrezhdaiushchego khromosomy deistviia ftorafura.

Chromosome damage induced by three antineoplastic drugs -- ftuorafur (Ft), 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine (FUdR) hase been studied in Djungarian hamsters cell line after 24 hours exposition with these agents before the fixation. Ft at a dose of 10 micron/ml induced aberrations in 56.7% of metaphases. 60.0% of aberrant metaphases were obtained in experiments with 0.1 micron/ml of 5 FU. FUdr at the same dose induced 24.0% of aberrant metaphases. The high frequency of chromatid breaks and gaps was typical for the mutagenic action of these fluorinated pyrimidines. The addition of Ft or 5-FU to the cell cultures 1--12 hours before fixation did not produce any significant chrosome damage, while further exposition with the drugs for 15--24 hours caused breaks in more than 50% of metaphases. Thymidine at a concentration of 1.0 micron/ml suppressed the chromosome breaking effect of Ft and 5-FU. The results obtained are in accordance with the idea that fluorodeoxyruidinemonophosphate is the ultimate mutagen for both Ft and 5-FU and that the aberrations observed are due to the lack of thymidine nucelotides caused by the former agents while DNA replication.