Phytohemagglutinin-stimulated leukocyte-conditioned medium induces differentiation in acute promyelocytic leukemia cells in vitro.

Six-day cultures of FCS and PHA-LCM-stimulated whole blood from a patient with acute promyelocytic leukemia (APL) were examined for differential cell count and chromosome karyotypes. It was found that both FCS and PHA-LCM could induce partial leukemic cell differentiation and maturation to macrophage in vitro, while PHA-LCM caused lymphocyte proliferation too. The absolute number of atypical blasts and neutrophils decreased in all 6-day cultures. The majority of the dividing cells (81.4%) contained the characteristic translocation for APL, t(15; 17) (q22; q11). Thus, these were members of the leukemic myeloid lineage, whereas some cells contained normal karyotypes, which could be lymphocytes.

Chromosome changes in a brain metastasis of a large cell lung cancer.

Direct chromosome preparations were made on a brain metastasis of a large cell lung cancer from a 46-year-old female patient. In the 169 cells examined, the modal chromosomes number was 73, and the majority (53.2%) of mitoses were in the near-triploid region. The tumor cells showed considerable heterogeneity in chromosome number and content. Chromosomes 3, 4, and 5 were the most frequently involved in aberrations. The mean number of unidentified marker chromosomes was five per mitosis.

Short-term effects of 1-nitropyrene on chromosomes and on oncogene/tumor suppressor gene expression in vivo.

In order to establish an animal model testing the effects of 1-nitropyrene in vivo at the oncogene level, we investigated the early biological effects of 1-nitropyrene in mice. The treatment of 6-8 week-old CBA/Ca mice with a single 30 mumol/kg body weight dose of 1-nitropyrene caused a significant increase in chromosome aberrations 48 hours after exposure. The aberrations were mainly of the euploid type. We also found elevated expression of the Ha-ras oncogene in the isolated total cellular RNA from the liver, lung, kidney, spleen and thymus. The highest increase was seen in the lung and it was also high in the spleen and in the thymus. There was a higher increase in the males than in the females in all organs. In this study we confirmed that early genetic alterations such as oncogene expression, can be examined not only in vitro, but also in vivo experiments.

Spontaneous lymphoma in an AKR mouse with dominance of 42 chromosomes.

The chromosome content of the lymphoma cells derived from various organ manifestations of an AKR female mouse with spontaneous lymphoma was investigated. It was found that the lymphoma cells were heterogeneous and the dominant subpopulation of the lymphoma cells contained 42 chromosomes. At least 8 subpopulations of the lymphoma were detected at the karyotype analysis, from which the 41XX; +15; 41XX; +18; 42XX; +15, +18 and 44XX; +5, +8, +15, +18 karyotypes were the most frequent aberrations. The frequency of the presence of various subpopulations was different also in the thymus, spleen and lymph nodes. The authors suggest that over the trisomy of chromosomes 15, other trisomies (e.g. gain of chromosome 18) can play a role in the AKR mouse lymphomagenesis.

Comparative chromosome examination of AKR mouse lymphoma after its i.p. transplantation with thymus- or spleen-derived lymphoma cells into hybrid mice.

A spontaneous AKR female mouse lymphoma was transplanted with its thymus cell suspension (10(6) cells i.p.) into AKR female mice. Lymph node cell suspension derived from one of the leukemic mice was injected (10(6) cells i.p.) into AKR females. The lymphoma cells "homing" to the thymus of one of the AKR females were suspended in Parker solution and 5 X 10(6) cells were given i.p. 5 (C3H X AKR) F3 hybrid mice (group 1). The lymphoma cells "homing" to the spleen of the same AKR female were also suspended, and 5 X 10(6) cells were injected i.p. into 5 (C3H X AKR) F3 hybrids (group 2). Chromosomes were prepared from the thymus and the spleen of two mice in both groups. The karyotypes derived from the hybrids of group 1 were compared to that of the group 2. It was found that the lymphoma cells "homing" to the thymus could be characterized by the trisomy of chromosome 15, while the lymphoma cells "homing" to the spleen had primarily the trisomy of chromosome 18. The results indicate that the thymus manifestation of the spontaneous AKR lymphoma is heterogeneous, and it contains at least two major subpopulations of the lymphoma cells.

A noninvasive method for determination of the sex and karyotype of the fetus from the maternal blood.

The noninvasive method presented, using an "air culturing" technique, is capable of enriching for fetal cells in lymphocyte cultures of maternal blood. Through a combination of Y-body fluorescence and chromosomal heteromorphisms in the maternal blood, the fetal cells can be detected and used for the prenatal diagnosis of chromosomal abnormalities and the sex of the fetus in both the first and the second halves of pregnancy.

Miller-Dieker syndrome and monosomy 17p13: a new case.

A 12-year-old boy is described with multiple anomalies and a de novo terminal deletion of 17p13. Based on clinical examination, the Miller-Dieker syndrome was diagnosed.

Increased number of chromosome aberrations in the peripheral blood culture of a retinoblastoma patient.

Chromosome studies were performed on blood lymphocytes from an eight-year-old patient whose left eye had been enucleated earlier because of retinoblastoma. GTG-banded karyotypes showed both numerical and structural chromosome aberrations, and the number of the patient's lymphocytes with chromosome aberration increased. It was concluded that retinoblastoma survivors need continuous control because of the increased risk of second primary tumors.

Chromosome examinations on six-hour cultures of unstimulated peripheral blood from some patients with childhood leukemia.

Six-hour cultures of unstimulated peripheral blood cells from patients with various types of childhood leukemias were examined for chromosome karyotypes. It was found that this method was suitable for the detection of characteristic chromosomal abnormalities in two cases of acute nonlymphoblastic leukemias (ANLL; FAB types M3 and M6) and in a case of chronic myelogenous leukemia (CML), but not in acute lymphoblastic leukemias (ALL). The results suggest the usefulness of this simple method (possibly in combination with the thymidine boost technique of Yunis) in the cytogenetic diagnosis of some types of leukemias.

A new translocation t(1;4;11) in congenital acute nonlymphocytic leukemia (acute myeloblastic leukemia).

A new translocation t(1;11;4)(1pter----1p32::11q23----11q13::4p16--- -4qter) was found in the peripheral blood of a patient with congenital acute myeloblastic leukemia (AML). It was concluded that this translocation may represent a new mutation, which caused the leukemia with very high leukocytosis, hepatosplenomegaly, leukemic infiltration of the majority of the organs, and a very poor prognosis.

Examinations concerning the development of lymphoma following transplantation i.p. of AKR mouse lymphoma cells into hybrid mice.

Authors used a mouse lymphoma line--originated from a spontaneous AKR lymphoma--for serial transplantation into AKR mice. The homogenizate of the thymoma was always transplanted i.p. into the same mouse strain. When the cells taken from leukemic AKR mice were transplanted into adult C3H/He mice, these did not cause leukemia in the recipients. However, it turned out that the lymphoma cells were able to proliferate in the F3 hybrids of AKR male mouse crossed with C3H/He female. The question then arose, whether the donor cells originated from the AKR mouse grew and caused the lymphoma, or the transplanted cells would induce the cells of the recipient to develop lymphoma. On the basis of the results it was established that the AKR lymphoma cells themselves started developing in the recipients, when they were transplanted into hybrid mice and the cells of the recipient did not. The identification of the transplanted cells was done by the presence of the Rb [4.15] metacentric marker chromosome. These cells were found in the thymus, the lymph nodes and in the developing ascites of the hybrid mice. Two kinds of cell types were found in the lymph nodes, one of them contained the marker, while other did not. The spleen cells were free of the marker chromosome. These data suggest that the thymus manifestation of the AKR mouse lymphoma is heterogeneous--it consists at least of two major types of tumor cells. One of them has affinity to the thymus and the lymph nodes, while the other to the spleen and the lymph nodes too.

Inhibition of lung damage caused by paraquat with lymphokines or cytokines.

Gramoxone, containing paraquat as an active ingredient can cause severe lung injury in both humans and experimental animals. Biologically active fibroblast-stimulating factors produced by lymphocytes and macrophages may be of importance in the development of interstitial fibrosis. In our present study we have attempted to inhibit the process of paraquat induced lung fibrosis by lymphokine-enriched supernatants from concanavalin A stimulated spleen cell cultures. It was found that adequate supernatant treatment significantly reduced PQ-induced lung injury and its associated inflammatory response.

Chromosomal aberrations and fetotoxic effects of atmospheric arsenic exposure in mice.

Fetal chromosomal damage and toxicity were investigated in mice exposed to the atmospheric concentrations of 28.5 mg m-3, 2.9 mg m-3 and 0.26 mg m-3 of arsenic for 4 h per day on the 9th, 10th, 11th and 12th days of gestation. On the 18th day, the fetuses were removed, and the following parameters were examined: the number of dead fetuses, retardation in growth, osteogenesis and chromosomal aberrations in liver cells. It was found that exposure to As2O3 at 28.5 mg m-3 caused fetotoxic effects and chromosomal damage, while the two lower exposures produced no significant changes with the exception of a slight decrease (9.9 and 3.1%, respectively) in fetal weight.

The preventive effect of prednisolone on the adrenal toxicity of cadmium.

The effects of a single dose of 3.3 mg/kg body weight i.p. or of a single dose of 0.2 mg/kg per os of cadmium and prednisolone on the adrenal weight and the thickness of the adrenal cortex were investigated in female mice. A significant increase was detected in the mean weight of the adrenals and the thickness of the adrenal cortex was significantly higher than the control value on days 1-3 following cadmium treatment. A dramatic decrease was observed in both adrenal weight and adrenal cortex thickness on day 4 following cadmium administration. No significant change occurred in the adrenals when prednisolone was given orally to mice following cadmium administration. This observation indicates a protective action of prednisolone on cadmium-induced adrenal toxicity.

Chromosome examinations on a six-hour culture of unstimulated peripheral blood from a patient with childhood erythroleukaemia.

A six-hour culture of unstimulated peripheral blood from a patient with childhood erythroleukaemia was examined for chromosome karyotype. The characteristic chromosomal abnormalities of erythroleukaemia del (5q) and monosomy 7 were found in this case together with a marker chromosome and other chromosomal abnormalities. The results suggest the usefulness of this simple method in the cytogenetic diagnosis of some types of leukaemias.

The effect of paraquat lung on mononuclear cells.

The mouse footpad swelling test was used to clarify the possibility of the induction of local cellular reaction with cell suspension of mouse lungs treated with paraquat in a syngeneous animal. Among the inbred strains used, the highest, statistically significant cellular reactivity was observed in C3H/He strain mice. These results suggest indirect evidence of macrophage activation in the lung toxicity of paraquat.

The effect of prednisolone on the foetotoxicity of cadmium in pregnant mice.

The effects of prednisolone was investigated on the foetotoxicity of cadmium. CFLP female mice were given a single i.p. dose of 2.5 mg cadmium (Cd) per kg body weight on day 5 or 9 of gestation. This treatment significantly decreased both the number of live foetuses and foetal weights on day 18 of gestation. Prednisolone (0.1 mg kg-1) given daily from the day of cadmium treatment death, prevented the effects of cadmium on foetal weights in both groups, and on the number of live foetuses when cadmium was given on day 9 of gestation. When Cd was given on day 13 of gestation similar treatment with prednisolone did not influence either litter size or the weights of 1-day-old pups.

Additional data on the mutagenic effect of dinitro-o-cresol-containing herbicides.

In in vivo experiments in mice it was studied, on the one hand, whether 1 year after treatment with dinitro-o-cresol (DNOC)-containing herbicide it was possible to detect any increase in chromosome aberrations in the bone marrow cells of the mouse, and on the other hand, to learn the frequency of chromosome aberrations in the subsequent generations when the treatment of the male animals with DNOC-containing herbicide was continued in each generation and when it was discontinued before mating. The chromosome aberrations of the bone marrow cells of the treated mice were demonstrated even 1 year after the treatment. After the treatment of the male animals was continued in each subsequent generation, the chromosome aberrations in the embryos increased, whereas when it was discontinued, it decreased in the subsequent generations.

Effect of dimethoate and O-demethyldimethoate on bone marrow cells of CFLP mice.

The organophosphorus pesticide dimethoate and its nonalkylating O-demethyl derivative were tested for their ability to induce chromosomal alterations in bone marrow cells of CFLP mice after ip administration. A single dose of 20 mg/kg dimethoate proved to be ineffective. However, doses of 60 mg/kg dimethoate or 69 mg/kg O-demethyldimethoate sodium salt significantly increased the aberration rates above those of the controls. The same effect was observed after a nontoxic dose of 690 mg/kg O-demethyldimethoate sodium salt. Considering the distribution of the several aberration types, these findings suggest that the alkylating properties of dimethoate only in part may be responsible for its cytogenetic activity.