Anton Brøgger

Apparently spontaneous chromosome damage in human leukocytes and the nature of chromatid gaps.

SummaryData are presented concerning the amount of apparently spontaneous chromosome damage, the types of aberration and their distribution among the human chromosomes, based on analysis of 1468 leukocyte metaphases from 50 subjects. The result was 0.046 constrictions/cell, 0.056 gaps/cell, and 0.048 breaks/cell. Clustering of damage was found in 3p, 16q and slightly in 1p and 2p, whereas the C, F and G chromosomes showed a shortage of damage.Chromatid gaps were studied by light and electron microscopy with two preparation procedures: spreading on a water surface and methanol/acetic acid fixation with air drying. With the former technique the gap appears to be bridged by chromosome material, whereas the latter leaves a discontinuity in the chromatid.ZusammenfassungDie vorliegenden Resultate betreffen die Anzahl anscheinend spontan erfolgter Chromosomenschäden, die Art der Aberrationen und ihre Verteilung auf die einzelnen Chromosomen. 1468 Metaphasestadien von 50 Personen wurden untersucht. 0.046 Einschnürungen/Zelle, 0.056 Gaps/Zelle und 0.048 Brüche/Zelle wurden gefunden. Gehäuft traten die Schäden in 3p, 16q, leicht erhöht in 1p und 2p und vermindert in C-, F-und G-Chromosomen auf.Chromatiden-Gaps wurden licht-und elektronenmikroskopisch mit zwei Präparationsverfahren untersucht: Spreitung auf Wasseroberflächen und Fixierung in Methanol/Essigsäure mit anschließender Lufttrocknung. Bei der ersten Methode scheinen die Gaps von Chromosomenmaterial überbrückt zu sein, während sich bei der letzteren eine Diskontinuität des Chromatids findet.

Caffeine-induced enhancement of chromosome damage in human lymphocytes treated with methyl-methanesulphonate, mitomycin C and X-rays

Abstract Two hypothese have been put forward in the literature to explain the synergistic effect of caffeine with several mutagens: ( 1 ) binding of caffeine to DNA, and ( 2 ) inhibition of DNA repair. Autoradiographic studies with 3 H- and 14 C-labelled caffeine did not support the binding hypothesis. Caffeine enchanced in a synergistic way the amount of chromatid breaks and exchanged induced in human lymphocytes with methyl-methanesulphonate (MMS), mitomycin C (MC) and X-rays. The results are best explained if caffiene inhibits a post-replication repair process, particularly the filling-in of gaps in the newly synthesized DNA.

A model for the production of chromosome damage by Mitomycin C

A model is presented, which is based on the idea that the chromosome damage induced by Mitomycin C results directly from repair or misrepair of DNA molecules responsible for the linear continuity of the chromosomes. Testing the model with human cells confirms the prediction that exchanges with complete joining occur between chromosome regions containing homologous, repetitive DNA. Most probably incomplete exchanges involve homologous, but unique DNA sequences. — Prerequisites determining the MC-induced aberration patterns are the distribution of the chemical due to compartmentalization, the somatic pairing of chromosomes, and the occurrence of repeated or unique DNA sequences. — The scoring of different classes of MC-induced chromatid aberrations (attenuation, constriction, gap, break) in alcohol/acetic acid-fixed chromosome has a limited value.

Psoralen/UVA treatment and chromosomes

SummaryFive psoriasis patients treated with 8-methoxypsoralen and UVA (PUVA) were studied by lymphocyte cultures at the 1st, 5th, 10th and 20th treatment and at a maintenance treatment 6 months later. Abnormal amounts of chromosome aberrations were not found, and the frequency of sister chromatid exchange (examined at the last treatment) was not increased. In vitro experiments with nanogram doses of psoralen (similar to plasma levels in patients) showed no increase in chromosome aberration or SCE frequency.The results indicate that therapeutic doses of PUVA have no clastogenic effect.ZusammenfassungLymphocytenkulturen von 5 Psoriasispatienten kamen zur Untersuchung, die mit 8-Methoxypsoralen und UVA (PUVA) behandelt worden waren. Die Untersuchungen wurden nach der 1., 5., 10. und 20. Behandlung und nach 6 Monaten zur späteren Wiederbehandlung durchgeführt. Es wurden keine abnormen Mengen von Chromosomenaberrationen gefunden und die Frequenz von Geschwisterchromatidaustausch (GCA) (untersucht nach der letzten Behandlung) war nicht erhöht. „In vitro”-Experimente mit Nanogramm-Dosen von Psoralen (entsprechend den Plasmaspiegeln der Patienten) ergaben keine Zunahme von Chromosomenaberrationen oder der GCA-Frequenz.Die Ergebnisse weisen darauf hin, daß therapeutische Dosen von PUVA keinen clastogenen Effekt besitzen.

No evidence for a correlation between behaviour and the size of the Y chromosome

Y chromosome variation has been studied in three groups of Norwegian males: 35 boys from an adolescent psychiatric hospital; 45 men from a hospital for hard‐to‐manage or dangerous, psychotic men; and 26 boys from two ordinary school classes.

Interchromosomal DNA-containing fibres in human cells.

SummaryInterchromosomal fibres were observed by light microscopy in metaphases of HeLa cells and human lymphocytes prepared by spreading on a water surface. Autoradiography after labelling with tritiated thymidine showed that the fibres contained DNA. They were resistant to pronase treatment.

Testicular neoplasms occurring in four brothers. A search for a genetic predisposition.

Four brothers who developed testicular neoplasms, one bilaterally, are described. Histologic examination showed four of the tumors to be seminomas and one to be a mixed germ cell tumor. Three of the brothers are alive. Apart from a late‐onset bladder carcinoma in their father and a pulmonary cancer in a maternal uncle, cancers were not recorded in the extended kindred. One patient, a sister, and the parents had normal frequency of sister chromatid exchange (SCE) and chromosome aberrations, whereas the two patients sampled after radiation showed increase in one or both. The father was found heterozygous in 12 and the mother in 8 genetic marker systems among 25 tested. For the blood group gene loci JK and MNSs, and the erythrocyte enzyme locus GPT the father had given the same allele to all three affected sons examined. The mother had given different alleles to the sons in all of her informative markers. On the model of a recessively acting susceptibility gene, only JK and GPT remained consistent with linkage without recombination. These investigations did not add support to a genetic etiology for the unusual family occurrence of testicular cancer. An apparent birth‐order effect on time at onset/diagnosis in this and published families suggests time‐limited environmental factors. Nevertheless, JK, MNSs, and GPT should be included in future testis cancer families to test the model of a “dominant” genetic predisposition.

Structural chromosome aberrations in lymphocytes from children with one to five years of total remission after chemotherapy of acute lymphoblastic leukaemia

Cytogenetic studies were made of 25 children (11 girls and 14 boys) with acute lymphoblastic leukaemia treated successfully with cytostatic agents and a reference group of children matched for age, sex and residence. The cytostatic treatment involved vincristine, prednisone, 1-asparaginase, methotrexate, 6-mercaptopurine for two to three years, and in a few cases cyclophosphamide, daunomycin and cytosine-arabinoside. No irradiation was given. Chromosome breakage and sister chromatid exchange (SCE) were not increased at one to five years after end of therapy. More cells with cytologically stable aberrations (translocations, deletions) were found among the patients, although an unexpected number of aberrant cells was also observed in the reference group.

Carcinogenesis testing of saccharin. No transformation or increased sister chromatid exchange observed in two mammalian cell systems

Abstract Saccharin was assayed in two mammalian cell systems for possible transforming or mutagenic effects. In the mouse embryo fibroblast C3H/10T 1 2 cells, saccharin was without transforming effects over a large concentration range. On transformed, but non-oncogenic C3H/10T 1 2 type I cells, a slight effect on transition to the growth pattern morphology of types II and III cells was found, but this was not accompanied by characteristic changes in plasma membrane structure when studied by scanning electron microscopy. In human lymphocytes, saccharin did not induce any sister chromatid exchange. Addition of a metabolic activation system did not change the sister chromatid exchange pattern as usually seen after positive control with 3,4-benzopyrene. Based on these studies, saccharin cannot be classified as a carcinogen, not even a weak one. Neither does it appear to be a mutagen.

Y chromosome types among 106 unrelated Norwegian males

Quinacrine mustard fluorescence microscopy of the Y chromosomes of 106 unrelated Norwegian males revealed one with none, 11 with one, 86 with two, and 8 with three brightly fluorescing segments in the long arm. Population studies of chromosomal variants including the different Y types may give further clues to the function of this constitutive heterochromatin, even if, so far, any phenotypical manifestation of the Y polymorphism, particularly as regards behaviour, has not been found.