Critical valuation of the subrenal capsule (SRC) assay and its use in experimental therapy.
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Biomedical subjects
Publications and source records attributed to C Nowak.
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Complete groups of animals can be economized by application of the Box-Wilson-method to experimental determination of an optimal dosage for a drug combination. It is possible to minimize the number of controls additionally by means of successive cumulation of the number of controls additionally by means of successive cumulation of control-dates of interest over the single experiments of the series required and to improve the estimation of the reference parameter. An example is given to explain the procedure of evaluation of an optimal dosage for the two-drug combination VP16/IFX. Side effects are taken into consideration. An advantage is proved for the combination against the single substances.
V 79 hamster cells were exposed to hypotonic culture medium or to hypotonic solutions of ammonium sulfate, sodium chloride, or trishydroxymethylaminomethane. Hypotonic treatment led in all experiments to a clear increase of chromosomal aberrations. Reasons for the aberrations observed may be directly induced DNA damage such as double strand breaks or a release of DNase after lysosomal damage because of the hypotonic treatment. Other reasons involved in the aberration production may be changes of the internal pH or damage of the chromosomal proteins.
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We have examined the possibility of transplanting syngeneic and xenogeneic tumor material below the renal capsule of normal, immunocompetent mice as a chemotherapeutic test model. Whereas the Lewis lung carcinoma in the syngeneic system was appropriated for the 6-day-test, only 56% of spontaneous C3H mammary carcinomas showed an increase in the size of the transplanted material. An individual sensitivity to the cytostatic agents as an expression of biological variability could be detected for primary C3H mammary carcinomas. Both, xenogeneic lines of human origin, established in nude mice, and fresh resection material from the clinic showed on the normal, immunocompetent mouse no time-dependent, reproducible growth of the transplanted material in control animals. However, growth is considered as a precondition for estimating the effect of therapy. The normal, immunocompetent mouse was in our experiments not suitable for application of the renal capsule assay in the 6-day-test as a recipient for xenogeneic transplantation.
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Human peripheral lymphocytes and Chinese hamster ovary cells were treated in the G1 phase of the cell cycle with the trifunctional alkylating agent trenimon (TRN) and post-treated with a single-strand specific endonuclease from Neurospora crassa (NE). TRN induces chromosomal aberrations of the chromatid type (CA) and sister-chromatid exchanges (SCE). NE post-treatment leads to an elevation of the frequencies of CA but not of SCEs. This indicates that TRN induced CA are the result of DNA double-strand breaks and that the SCEs originate from other types of lesions, most probably base damage.
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Post-treatment of mutagen-treated human peripheral lymphocytes with a single-strand specific endonuclease from Neurospora crassa leads to a significant elevation of the rate of structural chromosomal aberrations. Our results indicate that DNA double-strand breaks (DSB) are ultimate lesions for the formation of chromosomal aberrations in the G1 and G2 phase of the cell cycle and probably also in the S-phase. Post-treatment of X-irradiated G2 cells with polyethylene glycol (PEG) leads to an elevation of the frequencies of chromatid type aberrations. This result is taken as an indication that nucleases from PEG-damaged lysosomes transform lesions in X-ray damaged chromosomes to DSB. With respect to the origin of chromosomal aberrations, our results are in favour of the breakage and reunion hypothesis of K. Sax , and not of Revell 's exchange hypothesis.
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