The Effects of 1-Beta-D-Arabinofuranosylcytosine and Adriamycin on the Chromosomes of Cultured Human Lymphocytes

<p>A study of chromosome aberrations induced by 1-Beta-D-arabinofuranosylcytosine (Ara C) and Adriamycin (AM) in the chromosomes of cultured human lymphocytes was made. There were significant increases in the frequency of aberrations with increasing concentrations of both Ara C (2.5, 5.0 and 10.0 mug/ml) and AM (0.01, 0.05, 0.10 and 0.15 mug/ml). The frequency of aberrations induced by both drugs also showed a 'levelling off' above particular concentrations. For Ara C the effect of increasing treatment time was also studied. The frequency of aberrations increased significantly with increasing treatment times (2, 3 and 4 hrs) although no 'levelling off' in the number of aberrations was observed. The relationship between the frequency of the different types of aberrations induced by Ara C and AM was studied. AM allowed for a study of the relative frequency of chromosome versus chromatid aberrations and fragment versus exchange aberrations. There were always more fragments than exchanges, and always more chromatid aberrations than chromosome aberrations. Aberrations induced by Ara C were all of the chromatid fragment type. A study was made of the distribution of inter- and intra-chromosomal aberrations in relation to light and dark G banded chromosomes. Both drugs induced more aberrations in the light G bands than the dark G bands. Both drugs showed distinct clustering of aberrations in some regions of the chromosomes (hotspots), although the location of AM induced hotspots was different from the location of those induced by Ara C. The distribution of AM induced chromatid aberrations was different from the distribution of the chromosome aberrations, as were the distributions of the fragment and exchange aberrations. The different types of aberrations also differed in the number of AM induced aberrations per unit length between the p and q arms. There were more aberrations per unit length in the p arm than in the q arm for exchanges, whereas for fragments and chromosome aberrations the reverse was true. For chromatid aberrations, there was no significant difference in the number of aberrations per unit length between the p and q arms. Inter-individual differences in the frequency of AM induced aberrations were observed in the .AM dosage experiments. Also there was a suggestion that the distribution of Ara C induced aberrations was different for different donors. AM increased the frequency of sister chromatid exchanges. Comparable results were not sought for Ara C because after cells were exposed to Ara C they did not pass through an S phase of the cell cycle, as is the case for cells exposed to AM. The relevance of the present in vitro studies to cancer chemotherapy is briefly discussed.</p>

The Effects of 1-Beta-D-Arabinofuranosylcytosine and Adriamycin on the Chromosomes of Cultured Human Lymphocytes

<p>A study of chromosome aberrations induced by 1-Beta-D-arabinofuranosylcytosine (Ara C) and Adriamycin (AM) in the chromosomes of cultured human lymphocytes was made. There were significant increases in the frequency of aberrations with increasing concentrations of both Ara C (2.5, 5.0 and 10.0 mug/ml) and AM (0.01, 0.05, 0.10 and 0.15 mug/ml). The frequency of aberrations induced by both drugs also showed a 'levelling off' above particular concentrations. For Ara C the effect of increasing treatment time was also studied. The frequency of aberrations increased significantly with increasing treatment times (2, 3 and 4 hrs) although no 'levelling off' in the number of aberrations was observed. The relationship between the frequency of the different types of aberrations induced by Ara C and AM was studied. AM allowed for a study of the relative frequency of chromosome versus chromatid aberrations and fragment versus exchange aberrations. There were always more fragments than exchanges, and always more chromatid aberrations than chromosome aberrations. Aberrations induced by Ara C were all of the chromatid fragment type. A study was made of the distribution of inter- and intra-chromosomal aberrations in relation to light and dark G banded chromosomes. Both drugs induced more aberrations in the light G bands than the dark G bands. Both drugs showed distinct clustering of aberrations in some regions of the chromosomes (hotspots), although the location of AM induced hotspots was different from the location of those induced by Ara C. The distribution of AM induced chromatid aberrations was different from the distribution of the chromosome aberrations, as were the distributions of the fragment and exchange aberrations. The different types of aberrations also differed in the number of AM induced aberrations per unit length between the p and q arms. There were more aberrations per unit length in the p arm than in the q arm for exchanges, whereas for fragments and chromosome aberrations the reverse was true. For chromatid aberrations, there was no significant difference in the number of aberrations per unit length between the p and q arms. Inter-individual differences in the frequency of AM induced aberrations were observed in the .AM dosage experiments. Also there was a suggestion that the distribution of Ara C induced aberrations was different for different donors. AM increased the frequency of sister chromatid exchanges. Comparable results were not sought for Ara C because after cells were exposed to Ara C they did not pass through an S phase of the cell cycle, as is the case for cells exposed to AM. The relevance of the present in vitro studies to cancer chemotherapy is briefly discussed.</p>

ЦИТОГЕНЕТИЧНІ ПОШКОДЖЕННЯ ХРОМАТИДНОГО ТИПУ ТА ГЕНОМНІ ПОРУШЕННЯ У ЛІМФОЦИТАХ ОНКОЛОГІЧНИХ ПАЦІЄНТІВ З РІЗНОЮ ЛОКАЛІЗАЦІЄЮ ПУХЛИН ПРИ ПРОМЕНЕВІЙ ТЕРАПІЇ

The article showed the study of chromatid type aberrations and genome abnormalities in 65 cancer patients at the stages of radiotherapy depending on tumor localization. Оncogynecological patients (with cancer in female reproductive system), lung cancer patients and head and neck cancer patients were examined before treatment, in the middle and at the end of the radiotherapy course. The over-spontaneous level of chromatid type aberrations and genomic abnormalities in cancer patients before the radiotherapy start was noted. The highest level of chromatid type aberrations before treatment was observed in lung cancer patients. No significant changes in the level of chromatid aberrations in oncogynecological patients during the whole radiotherapy course were detected. In the middle of treatment there was a significant frequency increase of chromatid type aberrations in head and neck cancer patients compared with pre-radiotherapy values of these parameters. This increase disappeared at the end of the radiotherapy course. In contrast to oncogynecological cancer patients and head and neck cancer patients in the group of lung cancer patients there was a significant increase of chromatid type damage level from the beginning to the end of the radiotherapy. The accumulation of radiation-non-specific rearrangements was mainly due to chromatid fragments, and the level of chromatid exchanges remained unchanged during the radiotherapy. The frequency variations of genome abnormalities, such as hyperploids and endoreplications, fluctuated in all patient groups. Concerning the polyploid cells, a significant difference at all stages of the study was observed in oncogynecological patients. The research of chromatid type aberrations and genome abnormalities showed some different features in changes of these parameters depending on tumor localization. The obtained data complemented the knowledge about the general cytogenetic status of cancer patients and are important for determining the influence of such a factor as tumor localization on the formation and dynamics of radiation-non-specific chromatid type lesions and genomic abnormalities during a radiotherapy course.

Effects of 5-fluorouracil on the mitotic activity of onion root tips apical meristem

The effects of various concentrations of 5-FU on the mitotic activity of onion root tips apical meristem were investigated during 24-hour incubation in 5-FU and postincubation in water. The incubation in 5-FU caused a reversible inhibition of mitotic activity, and waves of the partially synchronised mitoses were observed during the period of postincubation. The most pronounced synchronisation of mitoses was obtained after incubation in 100 mg/l. 5-FU but the mitotic index of the resumed mitotic activity amounted to only one half of the control value. 5-FU was found to cause some cytological changes in meristematic cells such as enlargement of the nucleoli, change in the interphasic nuclei structure, appearance of subchromatid and chromatid aberrations and micronuclei. The effects of 5-FU on nucleic acids and the cell division cycle ace discussed and compared with the effects of 5-FUdR.

Interchromosomal distribution of gamma ray-induced chromatid aberrations in Chinese hamster ovary cells

Interchromosomal distributions of breakpoints from chromatid-type aberrations induced by gamma rays in Chinese hamster ovary (CHO) cells were analyzed. In most chromosomes the distribution was as expected from chromosome lengths for simple breaks or the respective relative corrected length in case of exchanges. There were deviations from expectation in a few chromosomes for chromatid breaks, interchanges, intra-arm intrachanges and inter-arm intrachanges. Especially interesting are the results concerning chromosomes 2 and 8, which were more often involved in exchanges than expected. An "exchange phenotype" for these chromosomes is proposed and possible explanations for the nonrandom distribution of chromosome breakpoints are presented.