Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic acid.

Allium vegetables (onions, leeks, chives) and in particular garlic have been claimed to have health-promoting potential. This study was conducted to get insight into the perspectives for monitoring the intake of garlic by a biomarker approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S-allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase resulting in the formation of S-allyl-l-cysteine. The latter compound is subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid (ALMA) and excreted into urine. The mercapturic acid was measured in urine using gaschromatography with mass spectrometry. Thus the intake of garlic was determined to check the compliance of garlic intake in a placebo-controlled intervention study. Results indicate that S-allyl-mercapturic acid could be detected in 15 out of 16 urine samples of garlic supplement takers, indicating good compliance. In addition, the intake of garlic was also monitored in a cross-section study of vegans versus controls in Finland, in which no differences in garlic consumption nor in ALMA output were recorded between vegans and controls. These data indicate good possibilities for further studies in the field of biomarkers to investigate the putative chemopreventive effects of garlic and garlic-containing products.

Prophylactic pretreatment of mice with hematopoietic growth factors induces expansion of primitive cell compartments and results in protection against 5-fluorouracil-induced toxicity.

The aim of this study was to expand the primitive and committed hematopoietic cell compartments in vivo in order to confer resistance of the blood cell forming system against the cytotoxic, cell cycle specific drug 5-fluorouracil (5-FU). Possible chemoprotective effects of such a pretreatment could result from increased numbers of hematopoietic cells, present before 5-FU administration. In addition, we hypothesized that an enhanced number of primitive and progenitor calls would result in a reduced cycling activity, ie, 5-FU sensitivity, of these same cells, due to normal physiological feedback loops. Administration of stem cell factor (SCF) plus interleukin-11 (IL-11) to mice was shown to result in expansion of the various immature cell compartments in marrow and, in particular, spleen. The total body content of the primitive cobblestone area forming cells (CAFC)-day 28 was increased to 140%, whereas the more committed cells (CAFC-day 7, erythroid and granuloid progenitors) were increased to 500%. This in vivo expansion resulted in a decreased 5-FU sensitivity of the hematopoietic system. In particular, mice that had received 5-FU 24 hours after discontinuation of growth factor pretreatment showed significantly less toxicity of committed cell stages. Compared with mice not pretreated, it appeared that in pretreated mice, 24 hours after 5-FU administration, the absolute number, but also the fraction of surviving CAFC, was much higher in both marrow and spleen. This was caused by a decrease in the cycling activity of all primitive cell subsets. To explore the possible use of this finding in a chemotherapeutic setting, we determined the interval between two subsequent doses of 5-FU (160 mg/kg) that was required to prevent drug-induced mortality. When control mice received a second dose of 5-FU 7, 10, or 14 days after the first, respectively 0%, 20%, and 80% survived. In contrast, 40% and 100% of mice that received SCF + IL-11 before the first dose of 5-FU, survived a second dose of 5-FU given respectively after 7 or 10 days. To assess whether chemoprotection in this setting could be ascribed to protection of the hematopoietic system, we transplanted a high number of normal bone marrow cells (sufficient to compensate for any hematopoietic deficiency) to normal and pretreated mice after they had been administered 2 doses of 5-FU, given 7 days apart. Bone marrow transplantation (BMT) could only rescue 50% of mice not pretreated, showing that a significant part of the mortality was because of nonhematologic toxicity. However, a BMT given to growth factor pretreated mice saved all mice, indicating that in this setting SCF + IL-11 had additional protective effects on cell systems other than hematopoiesis. In conclusion, our study showed fundamental knowledge about the behavior of primitive cells in vivo and has shown that manipulation of these and other cell compartments with appropriate growth factors may confer resistance against cytotoxic drugs.