High susceptibility to aflatoxin B1 and benzo(a)pyrene of BALB3T3 A31-1-1 cells expressing monkey CYP1A1.

Itoh, Susumu; Tagawa, Sanae; Sawada, Minoru; Kamataki, Tetsuya

doi:10.2131/jts.18.3_207

Cited by 2 publications

(1 citation statement)

References 13 publications

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“…However, CYPlAl appears to be neither constitutive nor routinely inducible in human liver (Murray et al 1993), which clearly limits the availability of this isozyme for research purposes. Hence, data are increasingly being generated on activation of mutagens and carcinogens (Aoyama et al 1989, Crespi et al 1989, Itoh et al 1993) and other aspects of substrate/inhibitor interactions for CYPlA (Fisher et al 1992, Eugster et al 1993, Tassaneeyakul et al 1993 using enzymes produced in heterologous expression systems.…”

Section: Introductionmentioning

confidence: 99%

Expression of human cytochrome P4501A1 (CYP1A1) in Saccharomyces cerevisiae inhibits cell division

Beresford

Taylor²,

Ashcroft³

et al. 1996

Xenobiotica

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1. Saccharomyces cerevisiae cells, genetically engineered to express human cytochrome P4501A1 (CYP1A1), have a mean doubling time of 5.8 h, which is considerably slower than that of control yeast cells that have undergone the same transformation process but with a plasmid lacking CYP1A1 cDNA (3.3 h). 2. A smaller reduction in the rate of cell division is observed in yeast cells expressing the closely related human P450, CYP1A2. No reduction is seen with plaice CYP1A, despite similar levels of P450 expression and enzyme activity (ethoxyresorufin O-deethylation) and no inhibition of growth is observed with yeast cells expressing higher levels of human CYP2D6. 3. Repeated culture of cells from a single CYP1A1 transformant colony results in a gradual loss of P450 expression and of CYP1A1-associated enzymatic activity over a 5-6 week period. In contrast, expression of human CYP2D6 by a single transformant colony is stable for at least 6 months. 4. The loss of CYP1A1 activity from transformed cells is accompanied by a return to normal growth rate, similar to that of control cells. 5. Inhibition of CYP1A1 enzyme activity during culture, by either type I (alpha-naphthoflavone), type II (ellipticine) or mechanism-based (1-(1'propynyl)pyrene) CYP1A inhibitors, does not affect growth rate, suggesting that some other property of human CYP1A1 protein is responsible for the growth inhibition observed.

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