Comparative morphological, cytospectrophotometric and immunochemical studies were carried out on 26 hepatocarcinomas of various malignancy excised from 21 F1 (CBA X C57B16) mice. It has been shown that in morphologically similar hepatomas the ploidy level and alpha-fetoprotein production intensity may vary markedly. Highly differentiated carcinomas usually of smaller sizes and homogeneous morphology have the modal class nuclei with tetraploid (6 cases) or octaploid (3 cases) DNA content. In moderately- and low-differentiated carcinomas the diploid class of nuclei significantly increased (in 4 out of 6 tumours). Large tumours morphologically heterogeneous according to the differentiation level had polymodal DNA distributions with predominating tetraploid nuclei (II cases).

Nuclear chromatin was separated into four fractions according to solubility in low (0.2 mM MgCl2, 10 mM Tris-HCl, pH 7.6) and high (2 M NaCl) ionic strengths after digestion of nuclear DNA with nucleases. In nuclear matrix DNA the ratio of active to inactive genes was always higher than that in the original total DNA, i.e., 25 times greater in rat liver nuclei. In DNA released from the nuclei into a low ionic strength buffer the active to inactive gene ratio was lower than in total DNA (3.7 times as low in case of rat liver nuclei). The amount of carcinogens in matrix DNA exceeded that of DNA soluble in a low ionic strength buffer (3-4 times in case of rat liver nuclei and 16 times in case of hamster embryo cells). The two other fractions occupied an intermediate position between the above said fractions of DNA. The experimental results suggest that the level of carcinogen-induced modifications may be increased in active genes, including transcribed protooncogenes.

A monolayer culture of mouse fibroblasts, line NIH/3T3, was transformed by DNA from human hepatoma cell line PLC/PRF/5. The resulting lines of transformed cells differ in their growth characteristics and are capable of producing tumors in nude mice. DNA of these cell lines was found to contain integrated sequences of human DNA and hepatitis B virus DNA. Analysis of transcription showed the amount of virus-specific RNA in the original cell line PLC/PRF/5 to be 20 times as large as in one of the transformed lines. Fragments of DNA of the transformed cells containing virus sequences were cloned, and 400,000 clones were obtained. A clone was identified the insert of which contains a portion of viral genome.

McA-RH 7777 hepatoma cell line has been cloned twice at a week's interval (analytical cloning). Alpha-fetoprotein (AFP) phenotypes of primary and secondary clones from 46 primary clones were analyzed. High interclonal variability exceeded the mutation rate by several orders. The interclonal differences have been also found in the variability rates.

An increased number of transcripts of c-Ha-ras, c-myc, c-sis and c-src protooncogenes has been detected in the chemically induced rat rhabdomyosarcoma related to the expression of that genes in normal muscle tissue of inbred rats. A degree of transcription elevation varies among the tested genes: c-src, c-Ha-ras and c-sis, c-myc.

The results of a complex family and population epidemiologic study of gastric cancer pointed to inheritance as an important factor of the incidence of this disease. However, there may be different combinations of genetic factors, on the one hand, and genetic and environmental ones, on the other, versus age and sex. This should be considered in conducting screening for families at genetic risk for stomach cancer and taking measures aimed at eliminating carcinogenic factors which increase the likelihood of familial cancer incidence. Such considerations should contribute to a certain degree to early diagnosis and prevention of the disease.

Two strains of P388 murine leukemia with acquired resistance to rubomycin (P388/rm) and its nitroxyl derivative ruboxyl (P388/rx). The rubomycin resistance has been developed by the 14th generation and ruboxyl one-by the 8th generation. The growth kinetic patterns and the cell cycle time of the parent and resistant strains were similar. An increased tumourogenicity of both resistant strains cells was found. The resistance development was accompanied by the appearance of the additional chromosome materials, namely of homogeneously staining region (P388/rx) and of double chromatin bodies (P388/rm). The partial recovery of sensitivity to rubomycin occurred during 36 generations (1 year). Simultaneously the genetic markers have been lost. The recovery of sensitivity to ruboxyl in this period was not observed. The obtained resistant strains possessed the multidrug resistance: the cross resistance of P388/rm and P388/rx to actinomycin D, Vinca alkaloids and colchicine was shown.

Cytogenetic examination of scrapings obtained from 42 patients with uterine bleeding was performed. A decrease in diploid cell level matched by a rise in that of aneuploid and aberrant cells was seen both in carcinoma and adenomatous hyperplasia of the uterine mucosa. A correlation was established between the level of aneuploid and aberrant cells, on the one hand, and degree of endometrial hyperplasia, on the other. Changes in karyotype in hyperplastic lesions of the endometrium are thought to be a factor predisposing to cancer development.

Seven cloned hybrid cell lines were obtained by fusion of OAV2a GFRT cells with lymphocytes of syngeneic rats. Three of the cell lines showed a reduced malignity when injected subcutaneously and were incapable of infiltrative growth when injected intraperitoneally. They were partially or totally devoid of colony forming activity in soft agar. Tumors which formed after injection of clone 2 cells revealed degenerative alterations and were infiltrated with lymphocytes. Separately floating rejected tumor fragments were vigorously attacked by macrophages.

Improved cytogenetic techniques allow for the identification of subtle chromosomal rearrangements associated with particular subgroups of monocytic leukemias. A detailed assessment of both quantitative and structural chromosomal defects is presented and clinical and prognostic value of the karyotypic pattern is discussed.

State and prospects of the drug cancer therapy are examined in the light of achievements of modern molecular oncology. Special attention is paid to the molecular genetic analysis of the appearance of individual and multiple cellular drug resistance in connection with amplification of definite genes as well as oncogenes. The idea about the possible role of oncogene activation as a universal cell reaction in response to an injury of environmental factors is advanced. It concerns both oncogenesis and induction of cancer cell drug resistance.

A possible role of chromosomal abnormalities in activation of cellular oncogenes is discussed. Data about the types of chromosomal aberrations characteristic of tumours and of expression of oncogenes localized in aberrant chromosomes are compared. For some oncogenes (c-myc, c-myb, c-abl, c-fes, c-fms) a more or less distinct correlation is observed between certain types of chromosomal abnormalities and increase of oncogene expression. On the contrary, one cannot observe such correlation for other group of oncogenes (c-fos, c-ets, c-mos, c-erb-A-1, c-sis, c-src). Chromosomal aberrations are probably one of the mechanisms of cellular oncogene activation during the carcinogenesis.