ADULT-SPECIFIC EXPRESSION AND INDUCTION OF CYTOCHROME P450(LPR) IN-HOUSE FLIES

Cytochrome P450(iota pr) is a xenobiotic metabolizing P450 that is fou nd in house flies (Musca domestica). To better understand the regulati on of cytochrome P450(iota pr), the effects of 21 potential monooxygen ase inducers were examined for their ability to induce total cytochrom es P450 and cytochrome P450(iota pr) levels in adult flies. Six compou nds caused induction of total cytochromes P450 per mg protein in adult susceptible (CS) house flies: ethanol (1.6-fold), phenobarbital in fo od (1.5-fold) or water (1.5-fold), naphthalene (1.3-fold), DDT (1.3-fo ld), xanthotoxin (1.4-fold), and alpha-pinene (1.2-fold). Six compound s were found to be inducers of cytochrome P450(iota pr): piperonyl but oxide in food (1.9-fold), phenobarbital in food (1.4-fold) and water ( 3.4-fold), clofibrate (1.3-fold), xanthotoxin (1.3-fold), methohexital (1.3-fold), and isosafrole (1.3-fold). Comparison of our results with house fly P450 6A1 indicates that there are specific inducers for eac h of these individual P450s as well as compounds that induce both P450 s. Total P450s were inducible by PB in CS house fly larvae, but not in LPR larvae. Immunoblotting revealed no detectable P450(iota pr) in co ntrol or PB-treated larvae in either strain. Thus, although total P450 s are inducible in the susceptible strain larvae, P450(iota pr), does not appear to be normally present or inducible with PB in larvae of ei ther strain. Northern blots of phenobarbital (in water) treated CS fli es indicated that there was a 4.2-fold increase in the P450(iota pr) ( i.e., CYP6D1) mRNA levels over the untreated flies. In the multiresist ant LPR strain there was no apparent induction of CYP6D1 mRNA by pheno barbital. Following phenobarbital induction, the level of CYP6D1 mRNA in the CS strain was about half of the level in the LPR strain. (C) 19 96 Wiley-Liss, Inc.