1. Cultured hepatic cells have reduced cytochrome P450 (CYP) activities in comparison with human liver, but the mechanism(s) that underlies this circumstance is not clear. We investigated the causes of this low CYP activity by analysing the activity, protein, mRNA and heterologous nuclear RNA contents of the most important CYPs involved in drug metabolism (1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5) in cultured human hepatocytes, and in HepG2 and Mz-Hep-1 hepatoma cell lines. 2. After 24 h of culture, hepatocytes retained most of their CYP activities and protein contents, but the mRNA decreased 20-fold. However, the mRNA content of most CYPs in 24-h hepatocytes was still 400-fold higher than in hepatoma cells. When we examined the transcriptional activity of the CYP genes, this decreased during culture time in hepatocytes and it was poor in hepatoma cell lines. 3. We investigated the abundance of key hepatic transcription factors that govern CYP transcription (C/EBP-beta: LAP and LIP, HNF-3alpha, HNF-4alpha, RXR-alpha) and observed that the expression of some factors was altered in the hepatoma cells. 4. In conclusion, the loss of biotransformation activity in cultured hepatic cells is caused by a decrease in CYP transcription, which correlates with an alteration in the expression of key transcription factors.

1. In previous studies (Boobis et al., 1985b) it was shown that a monoclonal antibody (MAb 3/4/2), raised against rat cytochrome P450 form c, reacts with an isoenzyme(s) of cytochrome P450 in human liver. It was predicted that the epitope with which this antibody reacts should be present on both isoenzymes of the P450IA gene sub‐family (the orthologues of forms c and d) in man (Edwards et al., 1987). 2. This antibody was used to probe 45 different samples of human liver, by the technique of Western blotting. With one exception, all of the samples contained immunoreactive protein, a single band at Mr 54,000 (orthologous to rat form d), which ranged in content from less than 0.5 to 33.5 pmol mg‐1 microsomal protein. The content of the human orthologue of form c was below 0.5 pmol mg‐1, the limit of detection of the assay. 3. Thirteen of the samples were from patients of known smoking status. Immunoreactive P450 content was 3.5‐fold higher, and phenacetin O‐deethylase activity was four‐fold higher, in the smokers than in the non‐smokers. 4. There was a highly significant correlation between the amount of immunoreactive cytochrome P450 and the high affinity component of phenacetin O‐deethylase activity in both smokers and non‐smokers. 5. It is concluded that the high affinity component of phenacetin O‐deethylase activity in man is catalysed by the orthologue of rat cytochrome P450d, and that this isoenzyme is inducible by cigarette smoking. 6. In a number of previous publications it has been suggested that there is an association between the poor metaboliser (PM) phenotype for debrisoquine and impaired phenacetin O‐deethylation. In the present study it was shown that not all subjects PM for debrisoquine are poor metabolisers of phenacetin.

Measurements of energetic electron beams generated from ultrahigh intensity laser interactions (I>10(19) W/cm(2)) with dense plasmas are discussed. These interactions have been shown to produce very directional beams, although with a broad energy spectrum. In the regime where the beam density approaches the density of the background plasma, we show that these beams are unstable to filamentation and "hosing" instabilities. Particle-in-cell simulations also indicate the development of such instabilities. This is a regime of particular interest for inertial confinement fusion applications of these beams (i.e., "fast ignition").

The application of high intensity laser-produced gamma rays is discussed with regard to picosecond resolution deep-penetration radiography. The spectrum and angular distribution of these gamma rays is measured using an array of thermoluminescent detectors for both an underdense (gas) target and an overdense (solid) target. It is found that the use of an underdense target in a laser plasma accelerator configuration produces a much more intense and directional source. The peak dose is also increased significantly. Radiography is demonstrated in these experiments and the source size is also estimated.

The generation of MeV electron and ion beams using lasers with intensities of up to 10 20 W cm Ϫ2 is reported. Intense ion beams with high energies ͑up to 40 MeV and to 3ϫ10 12 protons Ͼ5 MeV͒ are observed. The properties of these particle beams were measured in considerable detail and the results are compared to current theoretical explanations for their generation.

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Time-resolved x-ray spectra from solid targets irradiated by the VULCAN Petawatt laser focused to 1020Wcm−2 show that material at solid density is heated to temperatures above 500 eV to a depth of about 15 μm and for a duration of more than 30 ps. Modeling with the implicit hybrid plasma code LSP shows that the heating is sensitive to the laser prepulse through resistive inhibition of the laser accelerated electrons in the blow off layer.

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