In vitro activation of the human Harvey-ras proto-oncogene by aflatoxin B1

Carcinogenesis
J RileyG E Neal

Abstract

Activation of ras proto-oncogenes occurs frequently in vivo in chemically induced rodent tumours, including rat hepatomas induced by aflatoxin B1. This study examines the in vitro activation of a human ras gene by this mycotoxin. A plasmid containing the human Ha-ras proto-oncogene, together with a neomycin resistance gene (pECneo), was incubated in vitro with a microsomal system generating aflatoxin B1 8,9-epoxide. Subsequent transfection of the plasmid into mouse NIH 3T3 fibroblasts, followed by G418 selection and s.c. injection of surviving cells into immunodeficient mice demonstrated that the proto-oncogene had acquired transforming capacity. Although a single tumour resulted from similar treatment of incubated unconjugated plasmid, no tumours were produced by a secondary round of transfections using DNA from this tumour. Selective PCR amplification of the human Ha-ras gene in extracted tumour DNA followed by sequencing demonstrated the presence of G-->T transversions either at the first or middle base of codon 12 in tumours resulting from transfection with the aflatoxin-B1-modified pECneo plasmid, but this was not detected in the single tumour resulting from transfection with the unmodified plasmid. Thus, although a mutati...Continue Reading

Citations

Mar 5, 1999·Mutation Research·J S Wang, J D Groopman
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Aug 25, 2006·Nature Reviews. Cancer·Paraskevi A Farazi, Ronald A DePinho
Nov 5, 2013·Chinese Medicine·Patrick Ying-Kit YueKelvin Sze-Yin Leung
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Maryann E SmelaJohn M Essigmann

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