RELATIONSHIP BETWEEN HYDROCARBON STRUCTURE AND INDUCTION OF P450 - EFFECT ON RNA LEVELS

1. Exposure to simple aromatic hydrocarbons has been shown to induce P 450-dependent activities and the expression of particular P450 isozyme s in a manner related to the molecular structure of the inducing hydro carbon. In an attempt to identify the structural relationship controll ing P450 induction, the effect of hydrocarbon treatment on the RNA lev els for specific P450 isozymes was examined. 2. Rats were treated with daily injections of hydrocarbons (benzene, toluene, ethylbenzene, n-p ropylbenzene, m- and p-xylene) for 3 days, and the effects on specific RNA levels were examined by Northern blot hybridization. 3. Although P4502B1 mRNA was not elevated after hydrocarbon treatment, a significa nt elevation in 2B2 mRNA was observed after exposure to the larger aro matic hydrocarbons, ethylbenzene and m-xylene. It is interesting to no te that despite the substantial elevation of P4502B protein levels, on ly a small elevation of P4502B1 and 2B2 RNA was observed. 4. P4502C11 mRNA was only suppressed by ethylbenzene administration, despite the d epression of 2C11 protein levels by several hydrocarbons. 5. P4501A1 m RNA was not detectable and 2E1 mRNA was not changed by any aromatic hy drocarbon treatment investigated in this study. 6. The data indicate t hat the levels of mRNA species for a number of P450 isozymes are diffe rentially regulated by exposure to hydrocarbons, and that small change s in hydrocarbon size or isomeric structure can influence the levels o f these mRNA species.