Radiolabeled fluoromisonidazole (FMISO) is being investigated as an imaging agent for hypoxia in tumors and nonmalignant tissues in myocardial infarct or stroke. In this study in vitro cell cultures were used to characterize the oxygen dependency of FMISO uptake and to examine other modifying factors. The uptake of [3H]FMISO was measured in four cell lines in vitro: V-79, EMT-6(UW), RIF-1, and CaOs-1. The modifying effects of different O2 levels as well as cell growth state and concentration of glucose and nonprotein sulfhydryls were examined. In these cell types an O2 level between 720 and 2300 ppm inhibited FMISO binding by 50%, relative to binding under anoxic conditions. These values bracket the O2 level which confers full radiobiologic hypoxia, about 1000 ppm. Some bound label was released from cells in the first 1 to 3 h after a 3-h anoxic labeling with [3H]FMISO, but this does not represent tritium loss from the parent molecule. Cells from unfed plateau-phase cultures took up less [3H]FMISO than did exponentially growing cells incubated at comparable O2 levels. Reducing glucose to 1/10 or 1/100 of the usual concentration in medium had little effect on binding of micromolar levels of FMISO, except in V-79 cells, where reduced glucose levels were associated with increased FMISO accumulation. Adding cysteamine to the culture medium moderately increased FMISO uptake. We conclude that cell growth state, glucose, and nonprotein sulfhydryl concentrations affect FMISO binding, albeit less than varying O2 levels: anoxic/oxic binding ratios vary from 12.6 to 28 for the four cell types examined. Nonetheless these factors must be considered in evaluating the oxygen-dependent binding of this nitroimidazole in tumors or tissues.
In southeastern Australia, Fusarium crown rot, caused by Fusarium culmorum or F. pseudograminearum, is an increasingly important disease of cereals. Because in-crop control options are limited, it is important for growers to know prior to planting which fields are at risk of yield loss from crown rot. Understanding the relationships between crown rot inoculum and yield loss would assist in assessing the risk of yield loss from crown rot in fields prior to planting. Thirty-five data sets from crown rot management experiments conducted in the states of South Australia and Victoria during the years 2005 to 2010 were examined. Relationships between Fusarium spp. DNA concentrations (inoculum) in soil samples taken prior to planting and disease development and grain yield were evaluated in seasons with contrasting seasonal rainfall. F. culmorum and F. pseudograminearum DNA concentrations in soil prior to planting were found to be positively related to crown rot expression (stem browning and whiteheads) and negatively related to grain yield of durum wheat, bread wheat, and barley. Losses from crown rot were greatest when rainfall during September and October (crop maturation) was below the long-term average. Losses from crown rot were greater in durum wheat than bread wheat and least in barley. Yield losses from F. pseudograminearum were similar to yield losses from F. culmorum. Yield loss patterns were consistent across experiments and between states; therefore, it is reasonable to expect that similar relationships will occur over broad geographic areas. This suggests that quantitative polymerase chain reaction technology and soil sampling could be powerful tools for assessing crown rot inoculum concentrations prior to planting and predicting the risk of yield loss from crown rot wherever this disease is an issue.
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