The homogeneity of rat liver microsomal cytochrome P-448 activity and its role in the activation of benzo[a]pyrene to mutagens

The O-deethylation of ethoxyresorufin and the metabolic activation of benzo[a]pyrene to mutagens were determined in hepatic microsomal preparations from control and induced animals. An excellent direct correlation (r = 0.95) has been observed between ethoxyresorufin O-deethylase and the metabolic activation of benzo[a]pyrene to mutagens when the fraction of cytochromes P-450 present as cytochrome P-448 was altered by the administration of phenobarbitone and 3-methylcholanthrene alone or in combination with 9-hydroxyellipticine. The correlation between these activities was maintained following treatment of animals with Arochlor 1254, benzo[a]pyrene, benzo[e]pyrene, 7,12-dimethylbenzo[a]anthracene,2-anthramine and 2-naphthylamine.     

Regulation of phenolic catabolism in Rhizobium leguminosarum biovar trifolii.

In members of the family Rhizobiaceae, many phenolic compounds are degraded by the protocatechuate branch of the beta-ketoadipate pathway. In this paper we describe a novel pattern of induction of protocatechuate (pca) genes in Rhizobium leguminosarum biovar trifolii. Isolation of pca mutant strains revealed that 4-hydroxybenzoate, quinate, and 4-coumarate are degraded via the protocatechuate pathway. At least three inducers govern catabolism of 4-hydroxybenzoate to succinyl coenzyme A and acetyl coenzyme A. The enzyme that catalyzes the initial step is induced by its substrate, whereas the catabolite beta-carboxy-cis,cis-muconate induces enzymes for the upper protocatechuate pathway, and beta-ketoadipate elicits expression of the enzyme for a subsequent step, beta-ketoadipate succinyl-coenzyme A transferase. Elucidation of the induction pattern relied in part on complementation of mutant Rhizobium strains by known subclones of Acinetobacter genes expressed off the lac promoter in a broad-host-range vector.     

A protective monoclonal antibody recognizes a variant-specific epitope in the precursor of the major merozoite surface antigen of the rodent malarial parasite Plasmodium yoelii

The precursor of the major merozoite surface Ag (PMMSA) represents one of the principal molecules of the erythrocytic stages of malarial parasites. Previously we reported that mAb 302 recognizing the 230-kDa PMMSA of Plasmodium yoelii provided passive protection to mice challenged with this parasite. We now report that the protective capacity of mAb 302 is variant specific, affording protection against infection with only three of five P. yoelii lines. Immunoprecipitation analyses of their PMMSA revealed that the expression of the epitope recognized by mAb 302 also varied and correlated completely with the results of the passive protection studies. Although this specific determinant was not present on the merozoite Ag of all P. yoelii lines, the common expression of other B cell epitopes was noted by the demonstration of serologic cross-reactivity between these molecules. Furthermore, the relatedness of the genes encoding the PMMSA of several murine plasmodial strains and species was clearly shown in nucleic acid hybridization studies. Although strain-common and strain-variable epitopes have been observed in the PMMSA of the human parasite, Plasmodium falciparum, little is known concerning the variability of its biologically relevant epitopes. The current studies using the P. yoelii model system demonstrate that the epitope recognized by a protective mAb is strain variable. Because of the similarities between these antigens of P. falciparum and P. yoelii, this information may impact on the construction of an effective blood-stage malarial vaccine.     

The effect of an NADPH-regenerating system on biphenyl metabolism in isolated rat hepatocytes

Biphenyl 4-hydroxylation was studied in isolated rat hepatocytes. It was found that there was an inter-relationship between 4-hydroxylase activity and glucuronidase activity, removal of 4-hydroxybiphenyl by conjugation being necessary to stimulate a second phase of hydroxylation. Addition of an NADPH-regenerating system resulted in an initial depression of both processes, but later their activities were enhanced. This action could not be explained by the presence of non-viable cells.