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Fibroblast growth factor-binding protein 1 (FGFBP1) is a secreted chaperone that mobilizes paracrine-acting FGFs, stored in the extracellular matrix, and presents them to their cognate receptors. FGFBP1 enhances FGF signaling including angiogenesis during cancer progression and is upregulated in various cancers. Here we evaluated the contribution of endogenous FGFBP1 to a wide range of organ functions as well as to skin pathologies using Fgfbp1-knockout mice. Relative to wild-type littermates, knockout mice showed no gross pathologies. Still, in knockout mice a significant thickening of the epidermis associated with a decreased transepidermal water loss and increased proinflammatory gene expression in the skin was detected. Also, skin carcinogen challenge by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate resulted in delayed and reduced papillomatosis in knockout mice. This was paralleled by delayed healing of skin wounds and reduced angiogenic sprouting in subcutaneous matrigel plugs. Heterozygous green fluorescent protein (GFP)–knock-in mice revealed rapid induction of gene expression during papilloma induction and during wound healing. Examination of wild-type skin grafted onto Fgfbp1 GFP–knock-in reporter hosts and bone marrow transplants from the GFP-reporter model into wild-type hosts revealed that circulating Fgfbp1-expressing cells migrate into healing wounds. We conclude that tissue-resident and circulating Fgfbp1-expressing cells modulate skin carcinogenesis and inflammation.

The renally excreted amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo⁸dG) is a potential marker of oxidative DNA damage by reactive oxygen species. We have developed a high-performance liquid chromatographic (HPLC) method to determine oxo⁸dG in urine from humans and Wistar rats. First, 300 μl of filtered urine is prefractionated by solid phase extraction (BAKERBOND SPE C₁₈ Polar Plus column). Then, the HPLC separation of the fraction containing oxo⁸dG is performed using four HPLC columns (two cation exchange and two C₁₈ columns) in series with an automated column switching technique. Quantification of oxo⁸dG is performed by electrochemical detection (Coulochem II, ESA Inc.). Limit of detection was 0.4 nM oxo⁸dG. Recovery of oxo⁸dG added respectively in 11 or 8 concentration steps (range, 4–74 or 2–23 nM) to a pooled human or rat urine was 104.1 ± 4.3 or 104.5 ± 7.7%. Precision of sixfold analysis of a pooled human or rat urine carried out respectively on the same day was 2.2 or 2.4% relative standard deviation. Normal excretion rates of oxo⁸dG in healthy adult humans (five females, six males; body weight, 70.7 ± 11 kg) and male Wistar rats (body weight, 309 ± 13 g) were 281.7 ± 179.1 and 333.2 ± 47.4 pmol oxo⁸dG/day/kg weight, respectively. Copyright 2000 Academic Press.

DNA damage by reactive oxygen species is of special interest in the development of cancer and in aging. The renally excreted amount of 8-oxo-7,8-dihydro-2′-deoxyguanosine (oxo8dG) is a potential noninvasive marker of oxidative DNA damage. The respiratory chain of mitochondria is one source for the formation of reactive oxygen species. In the present study we investigated in Wistar rats (n = 7; mean body weight at start, 307.4 ± 11 g) the effect of an increased O2 consumption, i.e., energy expenditure, due to cold stress on the renally excreted amount of oxo8dG. First, the rats were housed for 4 days at 23.5°C (basic period, BP), and then for 6 days at 10°C (cold stress period, CSP), and finally for 3 days at 23.5°C (recovery period, RP). The O2 consumption (L O2/day/kg weight) was significantly (P < 0.0001) on average 50% higher in CSP (69.0 ± 3.9) than in BP (45.8 ± 4.8), and similar in BP and RP (44.3 ± 5.4). The average renal excretion of oxo8dG (pmol/day/kg weight) was significantly (P < 0.025) on average 13% higher in CSP (375.5 ± 27.7) than in BP (333.2 ± 47.4) and similar in BP and RP (331.8 ± 34.3). Maximum increase in oxo8dG excretion of on average 17% was on the third to fifth day of the CSP. This study reveals that an increase in O2 consumption of 50% resulted in a much lower increase in the renal excretion of oxo8dG.