The frequency of spontaneous and Mitomycin C (MMC)-induced sister chromatid exchange (SCE) was investigated in peripheral lymphocytes of 31 untreated patients with cervical cancer (stage 0:7 cases, stage I:9 cases, stage II:6 cases and stage III:9 cases), as well as of 7 untreated patients with myoma uteri and 16 healthy women. Factors affecting SCE frequency were also investigated. Age, smoking and atomic bomb exposure did not influence SCE frequency. However, a family history of cancer significantly increased MMC-induced SCE frequency in the cancer group. The mean spontaneous SCE frequency in the cancer group (9.83 +/- 1.74) was significantly higher than that in the myoma group (8.13 +/- 0.81) and healthy women (7.59 +/- 0.85). The mitomycin C-induced SCE frequency was also higher in the cancer group. Spontaneous and MMC-induced SCE frequency gradually increased with the progression of cervical cancer. All chromosome groups equally contributed to the increased SCE frequency in the cancer group. These results suggest that deoxyribonucleic acid of all chromosomes is damaged in patients with cervical cancer.

Cancer Research has changed substantially over the past several years since oncogenes were isolated from cancer cells. More than 40 oncogenes have been identified to date from tumor viruses and cancer cells. Many of the gene products seem related to signalling pathways that determine growth and differentiation of cells. This review attempts to summarize much of the currently available data and to gain future perspectives.

Recently accumulated data on the biology of the tumors of neuroblastoma group are reviewed. Histopathological classification system developed by Shimada et al, elevated levels of serum neuron-specific enolase and ferritin, and gene abnormalities including partial deletion of the short arm of chromosome #1 and N-myc gene amplification are discussed as well as their prognostic significance. Also, the current activities of CCSG (Childrens Cancer Study Group) neuroblastoma studies are briefly reported.

This article reviews the chemical modification of DNA (mainly proto-Ha-ras sequence) which causes mutation and induction of transforming activity. An initial chemical event caused by chemical carcinogens is modification of DNA with metabolically activated carcinogens. The chemical modification of DNA is thought to result in activation of oncogenes by mutation or reconstruction. The activated transforming oncogenes (mainly of the ras family, by point mutation) have been found in tumors induced by diverse carcinogens in vivo (reviewed briefly). Recently, results establishing that chemical modification of proto-oncogenes with carcinogens, such as benz (a) pyrene, acetylaminofluorene, Glu-P-1, 4NQO, and aflatoxin B1, induces transforming activity of the gene when transfected into NIH3T3 cells have been reported. The mechanism of activation of proto-Ha-ras by chemical modification has been investigated by RFLP (restriction fragment length polymorphism) assay and/or Southern blot analysis using synthetic oligonucleotides. Point mutations at codon 12 or 61 have been found. The correlation between the established chemistry of chemical modification of DNA with diverse carcinogens and activation of proto-oncogenes is discussed.

Retinoids are compounds that can elicit specific biological responses by virtue of their binding to and activating a specific receptor or a set of receptors. Retinoids produce various specific biological effects, including induction of terminal differentiation, regulation of cell proliferation, regulation of gene expression and regulation of the activity of specific enzymes in cells. In this article, the effects of retinoids on gene expression are reviewed. Among these effects suppression of myc expression and induction of EGF-receptor mRNA expression are considered to be closely related to regulation of cell proliferation. The effects of retinoids on cell growth are discussed on the basis of these two actions: myc mRNA suppression and EGFR mRNA induction. The mode of retinoidal action seems to be similar to that of steroids, as many investigators suggest. The molecular mechanism of retinoidal action is considered to be the formation of a retinoid-receptor complex and its interaction with regulatory elements of DNA. The possibility of application of the methodology used in the investigation of steroidal action to the study of retinoidal action is also discussed.

An immunohistochemical examination by the avidin-biotin-peroxidase complex method was carried out to assess the expression of oncogene-related products, i.e., ras p 21 protein, fes p 85 protein and epidermal-growth-factor (EGF) receptors, in human gastrointestinal malignancies. The presence of ras p 21, fes p 85 and EGF receptors was detected in 48%, 62%, and 62% of 29 colorectal carcinomas and in 65%, 65% and 40% of 20 gastric cancers, respectively. More than one oncogene protein was demonstrated in 18 of 29 colorectal carcinomas and in 10 of 20 gastric cancers. These results suggest that multiple oncogenes are important in the occurrence and progress of gastrointestinal malignancies.

Although meningiomas have been regarded as one of the benign brain tumors, cases showing clinically malignant behavior have been reported. For the purpose of detecting the possibility of predicting different biological behavior in meningiomas, eleven meningiomas were studied with the aid of flow cytometric (FMC) and cytogenetic techniques. Morphologically two cases were diagnosed as syncytial meningiomas and nine as transitional meningiomas. The former included one case (#5) of "syncytial poorly structured meningioma" (Zang et al.). In the FCM study seven out of eleven cases showed diploid (2C) or near diploid modal peaks with small amounts of tetraploid DNA (4C) cells. The remaining four cases had larger cell populations at 4C. Cytogenetically cells corresponding to 2C and near 2C peaks were also proved to be composed of diploid or hypodiploid cells in all of the eight cases studied. Chromosomal analyses revealed normal karyotypes in three. The remaining five hypodiploid cases had common chromosomal aberrations in G22, including missing chromosome 22 in four cases and 22 q-deletion in one. Nine cases grown in culture were also studied by FCM and were able to be maintained in culture from 14 days to 5 months. Close to the terminal stage of culture, most of the cases in culture tended to have higher cell population at 4C and the appearance of cells even at 8C (polyploidization). Similar changes were also obtained in cultured human fibroblast and seem not to be specific to this benign tumor. These results are discussed with reference to the previous reports from the point of view of patterns of FCM histograms from surgical specimens, degree of hypodiploidy, morphological behavior. Further studies, especially relating to basic cell kinetics are needed before clinical application can be made.