Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma

Following an i.p. dose of 150 mg x kg(-1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb/C mice. Time courses for tumour growth, intracellular levels of FdUMP, thymidylate synthase (TS) activity, and 5-FU in RNA were also determined, and the effects of a 9.5-min period of carbogen breathing, starting 1 min before drug administration, on MRS-detected 5-FU metabolism and tumour growth curves were examined. Both tumour variants generated MRS-detectable 5-FU nucleotides and showed similar initial growth inhibition after treatment. However, the growth rate of C26-B tumours returned to normal, while the sensitive C26-10 tumours, which produced larger fluoronucleotide pools, still showed moderate growth inhibition. Carbogen breathing did not significantly influence 5-FU uptake or fluoronucleotide production but did significantly enhance growth inhibition in C26-10 tumours. While both tumour variants exhibited incorporation of 5-FU into RNA and inhibition of TS via FdUMP, clearance of 5-FU from RNA and recovery of TS activity were greater for the insensitive C26-B line, indicating that these processes, in addition to 5-FU uptake and metabolism, may be important determinants of drug sensitivity and treatment respons

Discussion on detachment faulting and bimodal magmatism in the Palaeoproterozoic Willyama Supergroup, south-central Australia: keys to recognition of a multiply deformed Precambrian metamorphic core complex

Gibson & Nutman (2004) postulate that the Willyama Supergroup in the southern Curnamona Province contains a 1690-1670 Ma metamorphic core complex, and imply that this is relevant to the genesis of the Broken Hill Pb-Zn-Ag deposit. We contend that this is a model driven, speculative interpretation predicated upon unsupported assertions that conflict with substantial stratigraphic and geochronological data. Not only does the paper fail to demonstrate an early high-grade event and formation of a metamorphic core complex at 1690-1670 Ma, but it is also factually incorrect in several critical geological and geochronological aspects. The detachment concepts of Gibson & Nutman may appear persuasive, but only by omitting reference to a huge body of published and recent mapping and laboratory research, by companies, universities, and geological surveys, some of which are cited here. Surprisingly, Gibson & Nutman ignore much recent work (e.g. Page et al, 2004) to which one of them has contributed

Manganoan garnet rocks associated with the Broken Hill Pb-Zn-Ag Orebody, Australia

The original publication is available at www.springerlink.comThe Palaeoproterozoic Broken Hill Pb–Zn–Ag stratiform orebody is intimately associated with manganoan garnet-bearing rocks. On stratigraphic and chemical grounds it is argued that garnet-rich metasediments below, equivalent to and above massive sulphide were hydrothermal precipitates. Other manganoan garnet rocks formed during pre-metamorphic hydrothermal alteration, syn-metamorphic dehydration and reaction of manganese with prograde pelitic rocks, reaction between cataclastic manganese-bearing sulphide rocks injected along axial planes, shears and faults and pelitic wall rocks and reaction between dolerite dykes and sulphide rocks