Mitogen-Activated Lymphocytes: A Good Model for Characterising Lung Cyp1a1 Inducibility

in European Journal of Epidemiology (1997), 13(2), 177-83

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility ... [more ▼]

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility factor, generally evaluated on mitogen-activated lymphocytes after PAH induction, represents correctly the lung situation. Optimal experimental conditions were determined for evaluating, on both lymphocytes and lung tissue explants, the inducibility factor, defined as the ratio of EROD activity (CYP1A1-specific) to cytochrome c reductase activity (unaffected by PAH induction). Paired results for lymphocytes and lung tissue samples from 10 lung cancer patients were compared. A good correlation was observed between lymphocyte and lung tissue inducibilities (R = 0.809; p = 0.005). In conclusion, mitogen-activated lymphocyte inducibility is indicative of lung tissue inducibility and constitutes a good marker for evaluating individual PAH inducibilities. [less ▲]

Genetic regulation of hepatic steroid 16 alpha-hydroxylase activities in inbred strains of mice.

in Endocrinology (1984), 115

Steroid 16 alpha-hydroxylase activities and properties were studied in C57Bl/6J, 129/J, AKR/R, DBA/2J, C3H/I, and BALB/c mouse liver using four different substrates. The highest enzymatic activities were ... [more ▼]

Steroid 16 alpha-hydroxylase activities and properties were studied in C57Bl/6J, 129/J, AKR/R, DBA/2J, C3H/I, and BALB/c mouse liver using four different substrates. The highest enzymatic activities were measured in the female mice, with the exception of the 129/J females. As in the rat liver, the sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female mice took place at puberty. In the adult mouse liver, two steroid 16 alpha-hydroxylase activities (forms I and II) could be differentiated on the basis of their relative affinities for the various steroid substrates and their relative proportions in male and female mouse livers. In the immature mouse liver, no sexual differences could be detected, and the mice of both sexes presented phenotypes identical to those of the adult female. The adult 129/J females appeared genetically deficient with respect to the form I of the steroid 16 alpha-hydroxylase and presented a phenotype identical to that of the adult male mice of the various strains tested. Differences in hydroxylase activities between the C57Bl/6J and 129/J strains were investigated using standard genetic breeding protocols. Steroid 16 alpha-hydroxylase seemed to be inherited additively in the liver of the female mice obtained by crossing the C57Bl/6J male and the 129/J female or the 129/J male and the C57Bl/6J female. In the male mice, regardless of genotype, the observed phenotype was always identical to the two male parental types. Both hormonal and genetic regulations were responsible for the different phenotypes occurring in adult male and female C57Bl/6J and 129/J mouse livers. [less ▲]

Ontogenic development of steroid 16 alpha-hydroxylase as a tool for the study of the multiplicity of cytochrome P-450.

in European Journal of Biochemistry (1981), 120

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities ... [more ▼]

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities increase in parallel to the concentration of cytochrome P-450. Until puberty, they develop similarly in male and female rat livers. From the 40th to the 55th day, the four steroid 16 alpha-hydroxylase activities increase rapidly in the male rat liver. The sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female rats takes place around the 55th day. 2. In the adult rat liver, steroid 16 alpha-hydroxylase is supported by two forms of cytochrome P-450 (form I and form II), which differ in their relative affinities for the various steroid substrates, and by their relative proportions in male and female rat livers. These two forms of cytochrome P-450 are also present in the young male and female rat livers, but are roughly equal in proportion. The transition from the immature to the adult repartition of the two forms occurs during puberty and is correlated with the sexual differentiation of the steroid 16 alpha-hydroxylase activities. 3. During the critical phases of the rat ontogenic development, the in vitro interactions between benzo[a]pyrene and steroids were compared at the level of two rat liver monooxygenases: steroid 16 alpha-hydroxylase and aryl hydrocarbon hydroxylase. (a) In the immature male and female rat livers, progesterone 16 alpha-hydroxylase, and to a lesser extent, pregnenolone 16 alpha-hydroxylase are inhibited by benzo[a]pyrene. Progesterone 16 alpha-hydroxylase is also inhibited by metyrapone. (b) In the young rat, aryl hydrocarbon hydroxylase cannot be inhibited by steroids and appears to be supported by a single form of cytochrome P-450. The transition from the immature to the adult situation occurs around the 40th day. [less ▲]

Sex differences in the activity of different cytochrome P450 dependent steroid 16alpha-hydroxylases in rat liver

in Journal of Steroid Biochemistry & Molecular Biology (1980), 13

Steroid 16alpha-hydroxylase multiplicity in rat liver.

in Biochemistry, Biophysics and Regulation of Cytochrome. (1980)

Influence possible des facteurs nutritionnels sur l'ontogenèse de certaines formes de cytochrome P450.

Conference (1978, December)

Multiplicity of cytochrome P450 dependent steroid 16alpha-hydroxylase in the rat liver.

Conference (1978, June)