Zeitschrift fur Krebsforschung und klinische Onkologie. Cancer research and clinical oncology最新文献

160 chickens hormonally bursectomized before hatching, and 160 controls were twice given a dose of 10 mg 3,4-benzo(a)pyrene 2 weeks and 6 weeks after hatching. After 24 weeks the controls had developed muscle sarcomas at a significantly higher rate than the bursectomized animals (49.6--32.1%). The tumors were identified as malignant polymorphocellular rhabdomyosarcomas in light and electron microscopy. When the experiment was stopped after 27 weeks, the controls showed more tumors than the bursectomized chickens (65.1% versus 58.9%). The effect of bursectomy lies in a prolongation fo tumor latency. The frequency of metastases is equally decreased to a significant degree (41.7% versus 21.7%). These results are interpreted as an illustration of the disturbed equilibrium between the T and B cell responses.

Smears taken from eight probands with carcinoma in situ or invasive carcinoma of the cervix uteri have been stained with DDD and Fast Blue B. The extinctions microspectrometrically measured at 560 nm are directly proportional to the quantity of protein-SH-groups. The extinctions of the total cell (Eges) and of the cell nucleus (EK) are measured in 67 basal cells (BAS), 78 dysplatic cells (DYS), 122 undifferentiated cancer cells (UNIF) and 89 differentiated cancer cells (POLY). From BAS through DYS and UNIF to POLY EK increases by a total of 176%. In all four cell types investigated, linear correlations between EK and Eges have been found to occur with a probability of over 99%. The straight lines ascertained represent a relation between EK and Eges which is obviously very characteristic for each cell type, and it becomes apparent that the measuring points corresponding to each single cell are in each instance so close to the straight line that in most cases a differentiation of the three pathological cell types is possible even without a morphological criterion. The straight lines corresponding to BAS, DYS and UNIF start from a common origin, whereas the straight line corresponding to POLY branches off from the UNIF line only. This is in accordance with the formal genesis of pathological variants observed in the cervical squamous epithelium or in differentiated carcinomas of the squamous epithelium respectively.

30 female Wistar rats weighing between 70 and 90 g were fed for 8 months with 0,188% N-[4-(5-nitro-2-furyl)-2-thiazolyl] Formamide (FANFT). After this period a papillary tumor of the urinary bladder was demonstrable in each animal. Histological examination always revealed a transitional cell carcinoma with prevailing medium tumor stages; no distant metastases were found. The grade of malignancy was classified as medium and high. No significant statistical relationship could be ascertained between tumor stage and grade or between grade and weight, but a correlation was established between tumor stage and weight. After 12 months, 36/60 kidneys were found to be normal, whereas in 20/60 dysplasias and in 2/60 transitional cell carcinomas of the renal pelvis were observed; secondary hydronephrosis due to bladder tumors occured 4 times. Other organ changes were not noticeable.

A lifetime study in Swiss mice showed that a single 300microgram application of 7, 12-dimethylbenzanthracene (DMBA) once, or 300 or 30microgram DMBA once followed by 3.2 microgram phorbolester for 15 weeks induced a high number of skin tumors many of which regressed spontaneously. The regression occurred mostly early in the experiment, the number of appearing and regressing tumors following a cynical pattern. The incidence of regressions was only to a limited extent associated with tumor size, tumor duration and total number of tumors. Repeated DMBA treatment, 5 microgram twice a week induced the same types of tumors in larger numbers: with a smaller incidence of regressions and only if they were transient in nature, i.e., lasting less than 3 weeks. These occurred in animals which showed a large number of persisting tumors simultaneously, but which rarely displayed multiple regressions. The results indicate the occurrence of multiple steps of neoplastic transformation from hyperplastic lesions, benign regressing tumors, presistent tumors and frankly malignant ones, the incidence as well as biological behavior depending upon inducing treatment.

About 7000 animals of 65 different genotypes of the xiphophorine fish were treated with the direct acting chemical carcinogen N-methyl-N-nitrosourea (MNU; 10(-3)M; four times for 1 hour in two week intervals), in order to find out whether the susceptibility for development of fibrosarcomas and rhabdomyosarcomas is directly related to the genotype. A genotype specific susceptibility was found, ranging from zero to about nine percent. The highest susceptibles were found in certain backcross hybrids involving P.variatus/X.helleri-hybrids and X.helleri, as the recurrent parent. These genotypes were further analysed. Both P.variatus and X.helleri, as werr as their F1 proved to be insusceptible; while from the three backcrosses, which were tested, namely the BC1, BC4 and BC15, both the BC1, and the BC4, were susceptible, but the BC15 was insusceptible. The results are interpreted on the basis of the assumption that the differential susceptibility is a function of the type of control of a tumor gene (Tu-Fi-Rh) endogenous to P.variatus and involved in development of fibrosarcomas and rhabdomyosarcomas. Accordingly, in P.variatus and in the F1 the Tu-Fi-Rh is controlled by repressing genes (R-genes) linked as well as non-linked to Tu-Fi-Rh; because simultaneous mutation of both R-genes following treatment with MNU is an extremely unlikely event, these genotypes have an extremely low susceptibility. By contrast, in the BC1 and the BC4 the non-linked R-genes become eliminated and only the linked R-gene remains for repression of Tu-Fi-Rh; this condition confers a high degree of susceptibility, because one single mutation may lead to impairment of the R-gene and to Tu-Fi-Rh-mediated formulation of fibrosarcomas and rhabdomysarcomas. In the BC15, furthermore, also the Tu-Fi-Rh has become eliminated, resulting in a loss of the susceptibility. The results suggest that in the xiphophophorine fish the susceptibility for responding to MNU-treatment with the development of fibrosarcomas and rhabdomysarcomas is related directly to the genotype.

The homologons alkyl-acetoxymethyl-nitrosamines were tested for carcinogenicity in SD rats. All compounds were found to be carcinogenic and induced within the same time carcinomas of the forestomach. The total doses necessary for induction of tumors are related to the length of the alkyl chain and hence to the watersolubility. These results are discussed.

The chromosomal proteins of rat liver were studied by SDS-gel electrophoresis during the process of nitrosomorpholine-induced hepatocarcinogenesis, in the primary hepatomas thus obtained, and in their metastases. It was found that an increased proteolytic activity was present in liver homogenates from carcinogen-fed animals which caused differences between the nonhistone chromosomal proteins of control and carcinogen-treated livers. These differences disappeared in the presence of the protease inhibitor PMSF. In the primary hepatomas slight quantative changes were observed: an increased amount of two proteins of 43000 and 63000 daltons molecular weight, respectively, and a decrease in the histone subfraction H 1 degrees. In the metastases both quantative and qualitative differences were detected: a strong decrease in the protein bands corresponding to the contractile proteins alpha-tubulin, beta-tubulin, and actin; an increased content of the 63000 dalton protein; the appearance of new proteins of approximately 60000, 90000, and 120000 daltons molecular weight, and the complete disappearance of histone H 1 degrees.

The kinetics of nitrosation of dimethylamine (DMA) in aqueous perchloric acid solution have been studied using a differential spectrophotometric technique. The rate law is Initial rate = e[DMA]0 [nitrite]2 0 [H+]/(f + [H+])2 where [DMA]0 and [nitrite]0 represent initial stoichiometric concentrations. At 310.0 K and mu = 2.0 M, e = (2.2 +/- 0.2) X 10(-5) M-1 s-1 and f = (1.28 +/- 0.02) X 10(-3) M. The associated activation energy is 56 +/- 3 kJ mol-1. A clear inhibition of the nitrosation rate by ionic strength has been observed in which only the kinetic parameter (f) has an effective change. It is concluded that under the experimental conditions of this work only the dinitrogen trioxid is the effective carrier for the nitrosation.

During the period of 18 days after transplantation the uptake of 3H-thymidine into DNA was significantly increased in the spleen of Ehrlich ascites tumor-bearing Swiss and NMRI mice. Adenosine deaminase activity was within the control limits in tumor-bearing Swiss mice and significantly increased for the tumor-bearers of the NMRI strain. However, the increase in the DNA content, which is associated to splenic hyperplasia, was evident only for the Swiss strain. The time course of the retention of 3H-DNA revealed that the half life of spleen cells ranged from 41 to 46 h in normal and tumor-bearing Swiss mice and normal NMRI mice. For tumor-bearing NMRI mice the rate of cell depletion was significantly increased (t1/2 = 32h) compared with that found in normal NMRI mice (t1/2 =44 h). The mean survival time was 23.0 days for the tumor-bearing Swiss mice and 24.6 days for the NMRI mice. These data suggest that the immune responses were similar in both strains of mice, although cell kinetics was different in the spleen of tumor-bearing Swiss and NMRI mice.