Immunochemical assessment of the influence of nutritional, physiological and environmental factors on the metabolism of toluene.

Abstract

Factors influencing the metabolism of toluene were investigated in rats using monoclonal antibody (MAb) to cytochrome P450 (P450). At low toluene concentrations, P450 IIE1 was primarily involved in the metabolism of toluene, whereas P450 IIC11/6 was involved at high concentrations. A low-carbohydrate diet induced P450 IIE1 and resulted in an increase in toluene metabolism. The intake of fat did not influence the metabolism. A lowered protein intake decreased not only the total content of P450 but also the P450 IIC11/6. Fasting and ethanol consumption also enhanced toluene metabolism via the induction of P450 IIE1. The metabolic rate of toluene in adult male rats was 4-fold higher than in immature males and adult females at a high substrate concentration because of the high level of P450 IIC11/6 in adult males, whereas no difference was noted between adult and immature females. Although development did not influence toluene metabolism in males at a low substrate concentration, the metabolic rate in adult female rats was significantly lower than that of immature females and males; this may be due to the decrease in P450 IE1 with development. Diabetic status influenced toluene metabolism in rats by affecting several kinds of P450 isozymes. Toluene exposure also affected its own metabolism by increasing P450 IIE1 and P450 IIB 1/2, and decreasing P450 IIC11/6. A significant difference in toluene metabolism was observed among rat, mouse and human liver microsomes. Thus, when considering the factors affecting toluene metabolism, it is important to elucidate the change in specific P450 isozyme composition related to the modifications, and their affinities to toluene.