Helga Waksvik

Effects of age sex and genes on sister chromatid exchange

Sister chromatid exchange (SCE) was studied in cultured lymphocytes from a limited series of 21 like‐sexed twin pairs; 11 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The 18 subjects, who were between 57 and 61 years old, had an SCE mean value (x̄) of 8.0 whereas the 24 subjects between 33 and 39 years of age had a mean of 6.8. The difference was statistically significant (P<0.001). The effect of age appeared to be present in both sexes. No significant difference was found between females (x̄%7.3) and males (x̄%7.5), nor between smokers (x̄%7.3) and non‐smokers (x̄%7.4). Drug users had a slightly higher mean (x̄%7.9) than non‐users (x̄= 7.0) (P < 0.05). This trend was found in each age group. The within‐pair variance was slightly higher in DZ than in MZ pairs. The difference was not significant. We conclude that genetic factors are probably not a major source of subject variation in SCE mean 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.

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.

Studies of HPD: Chemical Composition and in Vitro Photosensitization

Photoactivated porphyrins are at present being evaluated for use in cancer therapy (Kelly and Snell, 1976; Dougherty et al., 1978). The method is based on two properties of particular porphyrins: Their tumor-localizing ability (Gomer and Dougherty, 1979) and their photodynamic effect (for a review see Moan and Christensen, 1980). Porphyrin photosensitization is also manifested in the skin of patients suffering from porphyrias.