ANALYSIS OF CADMIUM-INDUCED MUTATIONS ALTERING CONDITIONALLY DEFECTIVE CELL TRANSFORMATION BY MUSVTS110 (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

ANALYSIS OF CADMIUM-INDUCED MUTATIONS ALTERING CONDITIONALLY DEFECTIVE CELL TRANSFORMATION BY MUSVTS110 (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A686 1992. Unique Identifier : AIDSLINE ICDB/92683212
Heckman CA; Murphy EC Jr; UT M.D. Anderson Cancer Center, Houston, TX 77030

Abstract: A number of metals, including cadmium and nickel, are established carcinogens, but the mechanism by which they damage DNA is not well understood. For example, both are strongly clastogenic, but have proved negative or weakly mutagenic in prokaryotic assays. To study damage by carcinogens to mammalian genes, we developed a mutagenesis assay based on MuSVts110-infected NRK cells (6M2 cells). MuSVts110 is a mutant murine sarcoma virus conditionally defective for cell transformation. At high-growth temperatures, MuSVts110 is transformation-incompetent due to a frameshifting deletion between the viral gag and v-mos genes. At low-growth temperatures, however, MuSVts110 RNA can be spliced, allowing the translation of the v-mos region. Carcinogen-induced mutations to MuSVts110 DNA are detected by 'reversion' of 6M2 cells to the transformed state at 39 C. When cadmium was used as the potential mutagen, 6M2 revertants were induced in which the MuSVts110 gene product at 39 C, usually a truncated gag gene product termed p58 gag, was a 100-kD gag gene-mos gene fusion protein (termed P100gag-mos). No viral RNA splicing was detected at 39 C in these cadmium revertants, arguing that the 100-kD protein translated as a result of a frameshift mutation between the MuSVts110 gag and mos frames. More extensive deletions in MuSVts110 DNA (up to approx 300 nucleotides) were noted in other cadmium revertants. PCR-amplification and sequencing experiments are in progress on a panel of 6M2 cadmium revertants to determine the precise mutations induced and assess their biological effects.

Keywords: Cadmium Cell Line Cell Transformation, Viral/*GENETICS Chromosome Deletion DNA, Viral/GENETICS Gene Products, gag/GENETICS Genes, mos/GENETICS Mutagenicity Tests RNA, Viral/GENETICS Sarcoma Viruses, Murine/GROWTH & DEVELOPMENT/*GENETICS ABSTRACT
920830
M9281095

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