Showing papers in "Molecular and Cellular Biology in 1978"

11 – Mechanisms of DNA Excision Repair in Human Cells

Abstract: It is possible to distinguish three separate pathways for the metabolism of DNA: replication, recombination, and repair. This distinction is not absolute and, as demonstrated below, there are large regions of overlap. In this paper we would like to concentrate on the process(es) of DNA repair and to consider the question of their general biological role. There are two different excision repair pathways; the nucleotide excision pathway, and base excision (apurinic) repair. Our evidence suggests that the bulk of repair induced by polycyclic aromatic hydrocarbons (PAH's) in human cells comes via the nucleotide excision pathway.

10 – Cell Transformation and Mutability of Different Genetic Loci in Mammalian Cells by Metabolically Activated Carcinogenic Polycyclic Hydrocarbons

Abstract: Treatment of experimental animals with chemical carcinogens, including some polycyclic hydrocarbons, can result in the formation of malignant tumors. The process whereby some chemicals induce malignancy is as yet unknown. However, in a model system using mammalian cells in culture, it was possible to show that the chemical carcinogens induce malignant transformation rather than select for pre-existing tumor cells. In the process of the in vitro cell transformation, the normal cells, which have an oriented pattern of cell growth, a limited life-span in vitro, and are not tumorigenic, are converted into cells that have a hereditary random pattern of cell growth, the ability to grow continuously in culture, and the ability to form tumors in vivo. This stable heritable phenotype of the transformed cells is similar to that of cells derived from spontaneous or experimentally induced tumors. Such stable heritable phenotype changes may arise from alteration in gene expression due to a somatic mutation after interaction of the carcinogen with cellular DNA. In the present experiments we have shown that metabolically activated carcinogenic polycyclic hydrocarbons which have been shown to bind to cellular DNA induce somatic mutations at different genetic loci in mammalian cells and that there is a relationshipmore » between the degree of mutant induction and the degree of carcinogenicity of the different hydrocarbons tested.« less