The expression of cytochrome P450IIB1 in saccharomyces cerevisia results in an increased mutation frequency when exposed to cyclophosphamide

Stephen Matthew Black, Sian Ellard, Richard R. Meehan, James M. Parry, Milton Adesnik, Jean D. Beggs, C. Roland Wolf

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

A recombinant plasmid containing a full length cDNA encoding the rat cytochrome P450IIB1 under the control of the Saccharomyces cerevisiae ADC1 promoter was constructed and transformed into the yeast strain KYI 118. The encoded P450IIB1 protein was produced at a level of between 0.1 and 0.2% of total yeast cellular protein (0.068 nmol/mg total cellular protein). This protein was localized in the mkrosomal fraction and had activity towards the substrate benzyloxy-resorufin, the activity being 0.16 nmol resorufin produced/ min/mg microsomal protein. When exposed to the anticancer drug cyclophosphamide the mutation frequency, as determined by the development of resistance to the arginine analogue canavanine, increased in a dose-dependent manner over a control strain and was up to 16-fold higher at the highest doses used.

Original languageEnglish (US)
Pages (from-to)2139-2143
Number of pages5
JournalCarcinogenesis
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 1989

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research

Cite this