Regulation of Hemocytes in Drosophila Requires dappled Cytochrome b5

A major category of mutant hematopoietic phenotypes in Drosophila is melanotic tumors or nodules, which consist of abnormal and overproliferated blood cells, similar to granulomas. Our analyses of the melanotic mutant dappled have revealed a novel type of gene involved in blood cell regulation. The dappled gene is an essential gene that encodes cytochrome b5, a conserved hemoprotein that participates in electron transfer in multiple biochemical reactions and pathways. Viable mutations of dappled cause melanotic nodules and hemocyte misregulation during both hematopoietic waves of development. The sexes are similarly affected, but hemocyte number is different in females and males of both mutants and wild type. Additionally, initial tests show that curcumin enhances the dappled melanotic phenotype and establish screening of endogenous and xenobiotic compounds as a route for analysis of cytochrome b5 function. Overall, dappled provides a tractable genetic model for cytochrome b5, which has been difficult to study in higher organisms

Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China

Background: In vitro and in vivo studies suggest that selected strains of probiotic bacteria can form tight complexes with aflatoxin B 1 and other carcinogens. Objective: The aim of the present study was to determine whether administration of probiotic bacteria could block the intestinal absorption of aflatoxin B 1 and thereby lead to reduced urinary excretion of aflatoxin B 1-N 7-guanine (AFB-N 7-guanine), a marker for a biologically effective dose of aflatoxin exposure. Elevated urinary excretion of this aflatoxin-DNA adduct is associated with an increased risk of liver cancer. Design: Ninety healthy young men from Guangzhou, China, were randomly assigned to 2 groups; one group received a mixture of Lactobacillus rhamnosus LC705 and Propionibacterium freudenreichii subsp. shermanii strains 2 times/d for 5 wk, and the other group received a placebo preparation. The subjects provided 4 urine samples: at baseline, at 3 and 5 wk after starting the supplementation, and at the end of the 5-wk postintervention period. Results: The percentage of samples with negative AFB-N 7-guanine values tended to be higher in the probiotic group than in the placebo group during the 5-wk intervention period (odds ratio: 2.63, P = 0.052), and a statistically significant decrease in the concentration of urinary AFB-N 7-guanine was observed in the probiotic group. The reduction was 36% at week 3 and 55% at week 5. The geometric means for the probiotic and placebo groups were 0.24 and 0.49 ng AFB-N 7-guanine/mL, respectively, during the intervention period (P = 0.005). Conclusion: A probiotic supplement reduces the biologically effective dose of aflatoxin exposure and may thereby offer an effective dietary approach to decrease the risk of liver cancer. © 2006 American Society for Nutrition.link_to_subscribed_fulltex

Fecal and urinary excretion of aflatoxin B 1 metabolites (AFQ 1, AFM 1 and AFB-N 7-guanine) in young Chinese males

Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin B 1 (AFB 1) metabolites, aflatoxins M 1 (AFM 1) and Q 1 (AFQ 1) and aflatoxin B 1-N 7-guanine (AFB-N 7-guanine) that are produced by the predominant forms of cytochrome P450 enzymes responsible for the biotransformation of AFB 1. Fecal and urinary AFM 1, AFQ 1 and urinary AFB-N 7-guanine were assessed in 83 young Chinese males selected from a larger population (n = 300) based on detectable urinary AFM 1. The concentration of fecal AFQ 1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was approximately 60 times higher than that of AFM 1 (2.3 ng/g, IQR 0.0 to 7.3). In urine, the median AFQ 1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM 1 and AFB-N 7-guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15), respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had significantly higher fecal concentrations of AFQ 1 (p = 0.043) and AFM 1 (p = 0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the respective differences in urinary AFQ 1 and AFM 1 concentrations approached statistical significance (p = 0.054, p = 0.138). Our study demonstrates that AFQ 1 is excreted in urine and feces at higher levels than AFM 1, and feces are an important route of excretion of these AFB 1 metabolites. AFQ 1 should be further assessed for its predictive value as a marker for exposure and risk of dietary aflatoxins. © 2005 Wiley-Liss, Inc.link_to_subscribed_fulltex

Tissue and sex-dependent differences in CYP2A activities in hamsters

Three enzymatic activities of the CYP2A subfamily, coumarin 7-hydroxylase (COH), testosterone 15α-hydroxylase (T15αOH) and testosterone 7α-hydroxylase (T7αOH), were characterized in liver, kidney and lung microsomes from control, pyrazole (PYR), 3-methylcholanthrene (MC) and phenobarbital (PB) treated female and male Syrian golden hamsters. Sex-dependent changes in the enzymatic activities were found. Among control animals COH and T15αOH activities were higher in males. T7αOH activity was five times higher in female kidneys than in males. Inducers changed this metabolic profile. MC and PB were potent CYP2A inducers in extrahepatic tissues: significant increases were found in COH (5-fold) and T15αOH (12-fold) activities in female MC lung microsomes and T7αOH (7-fold) in MC male kidney microsomes. PB increased significantly activities of COH (5-fold), T15αOH (3-fold) and T7αOH (10-fold) in male kidney microsomes. All inducers significantly increased T7αOH activity in male kidney microsomes but decreased hepatic T7αOH activity in both sexes. PYR treatment decreased hepatic CYP2A activities. Anti-mouse CYP2A4/5 antibody inhibited COH activity by a variable extent depending on the tissue and pretreatment and recognised three 52-, 49-, 48-kDa bands in liver and two major bands in kidney (48 and 49 kDa) and lung (49 and 52 kDa) microsomes. COH and T15αOH activities correlated well with 49 kDa protein (r = 0.95 and r = 0.99, respectively) in lung microsomes. These results suggest that i) the inducibility and immunological characteristics of CYP2A activities in hamster tissues are clearly different compared with those found in mouse, ii) MC and PB are potent CYP2A inducers in extrahepatic tissues of hamsters, and iii) that extrahepatic CYP2A activities exhibit remarkable tissue- and sex-dependent differences in their response to chemical inducers