The two basic objectives of this research are first to study the quantitative relationship between specific carcinogen-modified nucleotides in a diploid human cell genome and the frequency with which mutant (HGPRT locus) or anchorage-independent cells are observed in the surviving cell progeny; and second, to use basic cytogenetic and gene transfer techniques to characterize the anchorage-independent human cell clones or emergent cell lines which are produced by our carcinogen treatment. We will determine whether the phenotypic traits in these cloned human cell populations (e.g. anchorage independence in soft agar growth as a cell line, ability of their DNA to transform NIH/3T3 cells tumorigenicity) are relatable to any consistently observed cytogenetic change, or dominant-recessive behavior in future cell hybridization experiments. Integrated analytical (HPLC), cellular (mutation selection, soft agar cloning , metaphase karyotyping) and molecular (DNA purification/transfection) techniques are used in these experiments.
Our aim i s to integrate biochemical observations of nucleotide modification and mutation induction with molecular studies of the transformed phenotype and its dominant/recessive behavior in order to develop an understanding of neoplastic transformation.
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