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PubMed1975

The human leukocyte test system. III. Premature chromosome condensation from chemically and x-ray induced micronuclei.

Premature chromosome condensation (PCC) was induced in human leukocytes in vitro by a bifunctional alkylating agent 2,5-bis-(methoxyethoxy)-3,6-bis-ethylene-imino-p-benzoquinone (A 139), bleomycin and X-rays. Analysis shows that PCC originates from micronuclei that have been slowed down in their cell cycles in respect to the main nuclei. The mitosing chromatin of the main nuclei induced PCC in the associated micronuclei. Morphologically the PCC was mostly of the S-phase type with the chromatin exhibiting a more or less pulverized appearance; in some experiments this was verified by incorporation of (3H) thymidine (TdR). In a few cases the PCC looked like G2-phase PCC with ladder-like chromosomes. GI-phase PCC was not found. PCC of the type described in this work may be used as an indicator of induced lagging of chromatin that can be the result of chromosomal aberrations or of nondisjunction.

Alkylating Agents↗
PubMed1979

[Quantitative aspects of the relationship of the antitumor activity and toxicity of diaziridinyl-sym. triazines to their physicochemical properties].

The experiments on rats have shown that there is a linear dependence of the logarithms of reciprocal molar toxic (LD50) and therapeutic (ED50) for sarcoma 45 doses of 6-oxyalkyl-amino-2,4-bis(I-aziridinyl)-sym-triazines and 6-(5-substituted-2,2-dimethyl-1,3-dioxan-5-yl)-amino-2,4-bis(I-aziridinyl)-sym-triazines upon the induction constants of substituents at tertiary carbon, the antitumor activity being more sensitive to the substituent effect compared with the toxicity. The dependence of the logarithms of reciprocal molar therapeutic (ED50 for sarcoma 45 and ED95 for Walker sarcoma) and toxic (LD50 and LD100) doses of the compounds, both synthesized by us and taken from the literature, upon the logarithms of their distribution coefficients in the octanol-water system (IgP) shows a parabolic character with the maximum effect at the extreme point of the parabola. The antitumor activity was more sensitive to a changed IgP than the toxicity.

Animals↗