Aberrant RNA metabolism in hamster embryo fibroblasts exposed to benzo(a)pyrene
A wide variety of carcinogens are known to form adducts with RNA and protein. These can accumulate in large quantities and persist into the time period when the carcinogenic lesion is fixed. These lesions introduce a variety of biochemical effects on RNA synthesis and degradation. A new parameter of RNA metabolism, by cells in culture, has been observed in which neo-quiescent and quiescent cells were observed to excrete Urd and Cyd into the culture fluid. This phenomenon is linked to the net degradation of RNA within the cell combined with the metabolic isolation of the UXP pool. Since it is known that an early effect of carcinogens on liver is degranulation of rough endoplasmic reticulum, the effect of B(a)P on excretion of nucleosides by hamster embryo fibroblasts was examined. At doses of 0.04 to 1.0 ..mu..M B(a)P, the cells are either partially arrested in growth or undergo lysis during the period when normal cells leave the G/sub 2/M period. B(a)P treated cells initiated the excretion process at the same time as control cells, but the rate of release was enhanced 2- to 4-fold. The lethal toxicity of B(a)P to cultured hamster embryo fibroblasts is dependent on both the state of the cells and the growth medium. In the presence of benzo(a)pyrene, all RNA specific activity values show a different pattern than the control. The aberration may arise from either asynchronous cell growth or by alteration of a biochemical event that regulates initiation of rRNA synthesis. Studies on the effects of B(a)P on RNA synthesis show the potential rRNA accumulation is affected, which may be due to a greater instability of synthesized rRNA rather than an inherent blockage of RNA synthesis. In view of these observations, early modification of regulation of ribosomal RNA synthesis provides another potential site that may be rate limiting in the initiation of carcinogenesis. (ERB)
- Research Organization:
- Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6941700
- Report Number(s):
- CONF-8010108-1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550301 -- Cytology-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CARCINOGENESIS
CELL CULTURES
CLEARANCE
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DATA
EMBRYONIC CELLS
EXCRETION
EXPERIMENTAL DATA
FIBROBLASTS
HAMSTERS
HYDROCARBONS
INFORMATION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUMERICAL DATA
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
RIBOSIDES
RNA
RODENTS
SOMATIC CELLS
SYNTHESIS
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES