Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin B sub 1 -induced rat liver tumors
- Massachusetts Institute of Technology, Cambridge (USA)
c-Ki-ras and N-ras oncogenes have been characterized in aflatoxin B{sub 1}-induced hepatocellular carcinomas. Detection of different protooncogene and oncogene sequences and estimation of their frequency distribution were accomplished by polymerase chain reaction, cloning, and plaque screening methods. Two c-Ki-ras oncogene sequences were identified in DNA from liver tumors that contained nucleotide changes absent in DNA from livers of untreated control rats. Sequence changes involving G{center dot}C to T{center dot}A or G{center dot}C to A{center dot}T nucleotide substitutions in codon 12 were scored in three of eight tumor-bearing animals. Distributions of c-Ki-ras sequences in tumors and normal liver DNA indicated that the observed nucleotide changes were consistent with those expected to result from direct mutagenesis of the germ-line protooncogene by aflatoxin B{sub 1}. N-ras oncogene sequences were identified in DNA from two of eight tumors. Three N-ras gene regions were identified, one of which was shown to be associated with an oncogene containing a putative activating amino acid residing at codon 13. All three N-ras sequences, including the region detected in N-ras oncogenes, were present at similar frequencies in DNA samples from control livers as well as liver tumors. The presence of a potential germ-line oncogene may be related to the sensitivity of the Fischer rat strain to liver carcinogenesis by aflatoxin B{sub 1} and other chemical carcinogens.
- OSTI ID:
- 6699731
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:3; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
AFLATOXIN
GENETIC EFFECTS
ONCOGENES
DNA SEQUENCING
TUMOR CELLS
AUTORADIOGRAPHY
CARCINOGENESIS
CARCINOMAS
DNA ADDUCTS
DNA HYBRIDIZATION
DNA POLYMERASES
LIVER
MOLECULAR BIOLOGY
PHOSPHORUS 32
RATS
ADDUCTS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GENES
GLANDS
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
MAMMALS
NEOPLASMS
NUCLEI
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
ORGANS
PATHOGENESIS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIOISOTOPES
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques