Biomedical subjects
Publications and source records attributed to K Mortelmans.
A number of phthalate esters and related chemicals were tested for mutagenicity in Salmonella typhimurium. The chemicals were tested blind in three laboratories by a preincubation modification of the Ames Salmonella/mammalian microsome test using S-9 prepared from Aroclor-induced rats and Syrian hamsters. All chemicals tested were judged to be nonmutagenic.
During the production of Intraglobin, an i.v. tolerable IgG-immunoglobulin preparation, fraction Cohn II is treated with beta-propiolactone. Thereby the IgG-molecules are chemically modified thus preventing an increase in secondary aggregates which could give rise to adverse reactions in the patients treated with the IgG-preparation. The safety tests described here neither showed any evidence for the presence of unhydrolysed mutagenic-beta-propiolactone in the final product nor that neoantigenic determinants had been created by the reaction of beta-propiolactone with the protein molecules.
Mutagenic activity of urines obtained from operating room personnel was assayed in the Ames Salmonella/mammalian microsome system using three strains of histidine-dependent S. typhimurium, TA1535, TA1538, and TA100. Two procedures were employed. In the first, 100- and 200-microliter aliquots of urine obtained from 28 subjects working in either scavenged or unscavenged operating rooms were tested. In the second, urine samples obtained from 13 physicians before and after starting an anesthesia residency, as well as 250-fold concentrates of these samples, were assayed. There was no statistically significant difference in urinary mutagenic activities between individuals working in scavenged and those working in unscavenged operating rooms. Furthermore, urines of anesthesiologists collected before and after beginning training had similar mutagenic activities. Only heavy smokers had mutagenic urine. It was concluded that the majority of operating room workers do not excrete mutagens in the urine.
UV-irradiated human fibroblasts in tissue culture were exposed to photoreactivating light in an attempt to demonstrate a light-dependent loss of thymine dimers from the acid-insoluble fraction of the DNA. The only experimental conditions in which this phenomenon was observed was if the cells were grown for at least 10 days in Dulbecco's modified Eagle's minimum essential medium. Such cells lost a maximum of between 10-30% of the thymine dimers from their DNA during illumination for 1 h. When cells were grown in a variety of other media the phenomenon was not observed. The present experiments do not discriminate between true enzymatic photoreactivation and a medium dependent photosensitization phenomenon that is not enzymatic in nature.
Crude extracts of normal human diploid fibroblasts and of human peripheral blood lymphocytes excise thymine dimers from purified ultraviolet-irradiated DNA, or from the DNA presumably present as chromatin in unfractionated cell-free preparations of cells that had been labeled with [3H]thymidine. Extracts of xeroderma pigmentosum cells from complementation groups A, C, and D also excise thymine dimers from purified DNA, but extracts of group A cells do not excise dimers from the DNA of radioactively labeled unfractionated cell-free preparations.
Studies were carried out to determine the effect of mutation in the host pol I gene on survival of ultraviolet (UV)-irradiated bacteriophage T4. Whereas a slightly reduced survival was observed in Escherichia coli strain P-3478 (pol A(1)) compared to strain W-3110 (pol A(+)), no such difference was observed in two strains isogenic except for the pol A gene. It was also shown that, whereas bacteriophage T4x is sensitive to UV irradiation, X irradiation, and treatment with methyl-methanesulfonate (MMS), phage T4v(1) is sensitive only to UV irradiation. The survival of damaged phage T4x is neither affected by the presence of the rec A, rec B, or pol A mutations in the host, nor is there evidence that phage T4 effects repair of rec A or pol A mutants previously treated with either UV or MMS.