Individual Variation in DNA Repair in Human Peripheral Blood Monocytes
The growing list of genetic and biological markers presently applied for predicting risk of human beings to manifest irreversible chemically induced disease is now legion. It includes at the cellular level such diverse endpoints as cytogenetics , mutagen/carcinogen metabolism, DNA damage and repair [2, 3], mutability, transformability , promotability, radiosensitivity, immunokinetics, and cell physiology. Yet, the list of suitable and accessible human tissues available is small, limited in practice to heterogeneous cultured skin cells of fibroblastic or epithelial morphology, peripheral blood lymphocytes , bone marrow, and organ autopsy or biopsy specimens. Each cell system has a common limitation in that baseline parameters which may not be stable or intrinsic are measured after some intervening culture manipulation. To circumvent this limitation, the studies to be discussed in this presentation have focused on the peripheral blood monocyte as a potential fresh ex vivo cell type in which to study selected endpoints [6, 7, 8]. Specifically, the extent of benzo[a]pyrene metabolism and unscheduled DNA synthesis after several DNA damaging treatments have been examined. These studies have lead to the realization that in vitro individuality in response to genetic damage is a complex function of both extra-genetic response to the agent(s) inflicting damage and possible genetically based peculiarities in processing of resultant lesions.
KeywordsAcetone Urea Hydrocarbon Fluorene Pyrene
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