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Biomedical subjects

G Chan

Publications and source records attributed to G Chan.

113 records · Page 7Linked to original sources

Comparison of cellular and whole-animal bioassays for estimation of radiation effects in the polychaete worm Neanthes arenaceodentata (Polychaeta).

The polychaete worm Neanthes arenaceodentata was used in experiments to determine possible relationships between short-term genotoxicity tests and reproductive and lethal consequences of exposure to ionizing radiation. Groups of juvenile N. arenaceodentata received one of four different radiation doses (2, 4, 8, and 16 Gy) to determine dose-effect estimates for chromosomal aberration induction, and groups of both adult and juveniles received one of seven different radiation doses (1, 4, 8.4, 46, 102, 500, and 1000 Gy) to determine dose-effect estimates for reproduction, mortality, and life span. Effects on reproduction and genetic material were observed at the lowest doses and in the same range; detrimental reproductive effects were observed at 1 to 4 Gy, and the frequency of chromosomal aberrations was significantly increased at 2 Gy. Only high doses resulted in acute mortality (greater than 500 Gy) and decreased life span (greater than 100 Gy). Dose-effect estimates for chromosomal aberration induction were dependent on radiation dose and on the stage of the cell cycle at the time of irradiation. Dose-effect estimates for reproduction were dependent on dose and the potential for repopulation of gonadal tissue. It is concluded that short-term genotoxicity test can be predictive of detrimental reproductive effects in those model systems for which basic cell kinetics and reproductive parameters are well known.

Animals↗

Structure of 5' regions and expression of phenobarbital-inducible rabbit cytochrome P450IIC genes.

To analyze phenobarbital-inducible genes in the P450IIC subfamily, fragments of rabbit genomic DNA containing portions of the P450IIC1 and P450IIC4 genes were isolated and the DNA sequences of the 5'-flanking regions and exons were determined and compared to that of the P450IIC2 gene. The sequences have consensus TATA motifs about 20 bp from the mRNA initiation sites as determined by single-strand nuclease mapping and primer extension. Sequences similar to those for proposed liver-specific regulatory factors, HNF-1 and CCAAT, are found in the P450 5'-flanking regions. A glucocorticoid response element is present in the P450IIC2 gene but is not conserved in P450IIC1 or P450IIC4. Other sequences similar to binding sites for AP-1, the octamer binding proteins, and SPH-1 are present. Except for the TATA motif, none of the potential regulatory sequences was conserved at the same location in the different genes. The P450IIC1 and P450IIC2 genes exhibited high similarity detectable by dot matrix analysis throughout the 700 bp of sequenced 5'-flanking region while the P450IIC4 gene exhibited high similarity to both P450IIC1 and P450IIC2 only for about -150 nucleotides from the RNA initiation site. Southern analysis using probes from the 5' region of the P450IIC4 gene suggests that there are at least three closely related members in the P450IIC4 subgroup in agreement with previous studies. After phenobarbital treatment, levels of P450IIC4 mRNA increased about fourfold, as measured by dot blot hybridization with a P450IIC4-specific oligonucleotide probe or by single-strand nuclease mapping of the 5' end of the mRNA, indicating that the P450IIC4 gene characterized in this study is responsive to phenobarbital. Phenobarbital treatment of rabbits increased in vitro transcription of RNA for both the P450IIC1/2 and P450IIC4 gene subgroups but only slightly and transiently for the constitutive P450IIC3 gene.

Amino Acid Sequence↗

Phototherapy and photopharmacology.

The activation of 8-methoxypsoralen (8-MOP) by long-wavelength ultraviolet A light (UVA, 320-400 nm) induces the formation of interstrand cross-links in DNA. Psoralen plus UVA (PUVA) is widely used in the treatment of psoriasis, a hyperproliferative disease of the skin. A new psoralen plus UVA therapy has been developed in which the 8-MOP-containing blood of cutaneous T cell lymphoma (CTCL) patients is irradiated with UVA light extracorporeally (i.e., extracorporeal photopheresis). The first group of patients had the leukemic variant of CTCL. A regimen of two treatments on successive days at monthly intervals produced a clinical response in eight of 11 patients. In this review the properties of several psoralens (both naturally occurring and synthetic derivatives) are compared, using several assays (DNA cross-linking, inhibition of lymphocyte response to mitogen stimulation, and cell viability). The development of a panel of monoclonal antibodies that recognize 8-MOP-modified DNA is also described. These antibodies have been used to quantitate 8-MOP photoadduct levels in human DNA samples. In addition to the psoralens, the light activation of two other compounds, gilvocarcin and an insulin-psoralen conjugate, is described.

Animals↗