8-Hydroxyguanine (8-OH-G) was discovered in 1983 in our laboratory at the National Cancer Center Research Institute, Tokyo. Since it could be formed in DNA not only in vitro but also in vivo by oxygen radical forming agents, we immediately hypothesized the importance of this discovery in connection with its biological consequence. Further intensive efforts by us from 1983 to 1990 confirmed that 8-OH-G is a highly significant oxidated DNA lesion involved in mutation and/or carcinogenesis in mammals, including humans. With the subsequent entry of many investigators to this research field the number of publications on 8-OH-G increased exponentially, reaching more than several thousands by the end of 2005. In this article, a summary is given of the important works carried out in the early days, and further notable contributions by many investigators are reviewed, focusing on 8-OH-G in the mammalian system. A special emphasis is given to research on knockout mice that are deficient in genes involved in the repair systems of the 8-OH-G lesion. Lastly, our own recent work is summarized involving a one-year carcinogenesis study of Ogg1 (the gene for 8-OH-G specific glycosylase/AP lyase) knockout mice that have been exposed to oxidative stress.
The blue pigment of cornflower, protocyanin, has been investigated for a long time, but its precise structure was not entirely explained until recently. The molecular structure of the pigment was recently shown to be a metal complex of six molecules each of anthocyanin and flavone glycoside, with one ferric iron, one magnesium and two calcium ions by X-ray crystallographic analysis. The studies provided the answer to the question posed in the early part of the last century, "why is the cornflower blue and rose red when both flowers contain the same anthocyanin?" This work was achieved on the basis of the results of long years of the studies made by many researchers. In this review, the author focuses on the investigations of the blue metal complex pigments involved in the bluing of flowers, commelinin from Commelina commusis, protocyanin from Centaurea cyanus, protodelphin from Salvia patens and hydrangea blue pigment.
Hepatic stellate cells (HSCs) are vitamin-A storing collagen-producing cells in hepatic lobules. The three-dimensional structure of HSCs has been demonstrated with the Golgi method, the maceration method for scanning electron microscopy, and confocal laser scanning microscopy. Many thorn-like microprojections or spines extend from the subendothelial processes and make contacts with hepatocytes. One HSC entwines two or more sinusoids and about 20-40 hepatocytes to create a cellular unit, `the stellate cell unit' or `stellon'. The Space of Disse is defined as the space between stellate cell-endothelial cell complex and hepatocytes. Intralobular heterogeneity of HSCs is assessed. HSCs develop from mesenchymal cells in the septum transversum. The developmental process of HSCs is reproduced partly in culture. In the lamprey abundant vitamin A is stored not only in HSCs, but in the fibroblast-like cells in the various other splanchnic organs. In vertebrates, the existence of both conventional fibroblast system in somatic tissues and vitamin A-storing cell system in splanchnic organs is suggested.
F1-Ay mice between RR (aabbCC) and C57BL/6J-Ay (AyaBBCC) have a much darker yellow coat color than do C57BL/6J-Ay. Quantitative trait locus (QTL) analysis was carried out to identify genes responsible for the darker modification of the yellow coat color (this has been traditionally termed "sable"). A significant sable QTL was identified on chromosome 1 (Dmyaq4, LOD score 15.5 for lightness, and 13.4 for color difference), in a chromosomal position similar to that of Dmyaq2, a sable QTL previously identified in C3H/HeJ. Another significant sable QTL was identified on chromosome 4 (Dmyaq5, LOD score 5.6 for lightness, and 4.3 for color difference) near the tyrosinase-related protein 1 (Tyrp1) locus. The effect of Dmyaq5 was significant only in the presence of the RR allele at Dmyaq4, suggesting that the Dmyaq4 (as well as Dmyaq2) is a novel coat color gene that may act up-stream of Tyrp1 signaling to increase eumelanin production.