[Hepatoblastoma, Etiology, Case Reports]. / Hepatoblastom, etiologie, kazuistiky.

Hepatoblastoma is an uncommon malignant neoplasm in general, yet, it is the most common liver malignancy in children with the incidence about one per milion children. This type of liver tumor usually occurs before the age of three years. The etiology of hepatoblastoma remains unknown. However, there are some genetic conditions known to be associated with an increased risk of developing hepatoblastoma such as Beckwith-Wiedemann syndrome, hemihypertrophy, APC-associated polyposis, α-1-antitrypsin defficiency and some metabolic disorders including tyrosinemia, galactosemia and glycogen storage disease type 1. There is a higher risk of hepatoblastoma in children with very low birthweight, children who acquire hepatitis B at an early age and children with congenital biliary atresia.

Frequency of chromosomal aberrations in Prague mothers and their newborns.

The capital city of Prague is one of the most polluted areas of the Czech Republic. The impact of air pollution on the level of chromosomal aberrations was systematically studied: analyses were performed using fluorescence in situ hybridization (FISH) with whole-chromosome painting for chromosomes #1 and #4. In the present study, we analyzed the levels of stable (one-way and two-way translocations) and unstable (acentric fragments) chromosomal aberrations in 42 mothers living in Prague and in their newborns. The average age of the mothers was 29 years (range, 20-40 years). Blood samples were collected from October 2007 to February 2008. The average levels of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) and benzo[a]pyrene (B[a]P) in respirable particles (PM2.5), as determined by stationary monitoring, were 21.0+/-12.3 ng/m(3) and 2.9+/-1.8 ng/m(3), respectively. We did not observe any effect of either c-PAH or B[a]P exposure on the genomic frequency of translocations (per 100 cells, F(G)/100) in either group due to their similar exposure during the winter months. The mean values of F(G)/100 representing stable aberrations were 0.09+/-0.13 vs 0.80+/-0.79 (p<0.001) for newborns vs mothers, indicating a significant increase of F(G)/100 with age. On the other hand, the frequency of unstable aberrations did not differ between the two groups. Our results demonstrate how the patterns of different types of aberration differed between newborns and mothers: we observed 64.3% unstable aberrations and 35.7% stable aberrations in newborns vs 19.7% and 80.3% in mothers, respectively. Our results indicate that after birth the frequencies of aberrations are very low and that the aberrations are represented mainly by acentric fragments. The changes observed in mothers show a shift to stable aberrations represented mainly by two-way translocations. The mother's age affected the level of aberrations in newborns: the group of children born to older mothers (31-40 years) had significantly increased F(G)/100 levels.

Effect of maternal tobacco smoke exposure on the placental transcriptome.

Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious neonatal health problems and chronic lifelong disabilities for the children (e.g., mental retardation, learning problems). To study the effects of tobacco smoke on the placental transcriptome, we performed gene expression profiling on placentas from women exposed to tobacco smoke in pregnancy (N = 12) and from those without significant exposure (N = 64). Gene expression profiles were determined by Illumina HumanRef-8 v2 Expression BeadChips with 18,216 gene probes. Microarray data were normalized by quantile method and filtered for a detection P-value <0.01. Differential gene expression was determined by moderated t-statistic. A linear model was fitted for each gene given a series of arrays using lmFit function. Multiple testing correction was performed using the Benjamini and Hochberg method. Abundant levels of transcripts were found for genes encoding placental hormones (CSH1, CSHL1), pregnancy-specific proteins (PSG3, PSG4, PAPPA), and hemoglobins (HBB, HBG, HBA). Comparative analysis of smokers vs nonsmokers revealed the differential expression of 241 genes (P < 0.05). In smoker cohort, we detected high up-regulation of xenobiotic genes (CYP1A1, CYP1B1, CYB5A, COX412), collagen genes (e.g., COL6A3, COL1A1, COL1A2), coagulation genes (F5, F13A1) as well as thrombosis-related genes (CD36, ADAMTS9, GAS6). In smokers, we identified deregulated genes that show tissue non-specific induction and may be considered as general biomarkers of tobacco smoke exposure. Further, we also found genes specifically deregulated in the exposed placentas. Functional annotation analysis suggested processes and pathways affected by tobacco smoke exposure that may represent molecular mechanisms of smoke-induced placental abnormalities.

Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part II. Oxidative damage.

Oxidative damage to macromolecules may have numerous negative health consequences. We measured oxidative damage to DNA, proteins and lipids in 80 newborns and 79 mothers, analyzed the effect of mother's tobacco smoke exposure on oxidative stress, and assessed correlations between oxidative stress markers and bulky and PAH (polycyclic aromatic hydrocarbons)-specific DNA adducts. Mean levels (+/-S.D.) of 8-oxodeoxyguanosine (8-oxodG) per 10(5) dG in the placenta were 2.85+/-0.78; we did not see a difference between 8-oxodG levels in newborns born to mothers exposed and unexposed to tobacco smoke. Protein carbonyl levels, a marker of protein oxidation, were comparable in the umbilical cord and in maternal venous blood plasma (17.4+/-3.2 and 17.6+/-4.2nmol/ml plasma in newborns and mothers, respectively, p=0.66). Lipid peroxidation measured as levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) in plasma was significantly higher in newborns than in mothers (362+/-129 and 252+/-130pg/ml in newborns and mothers, respectively, p<0.001). We did not find any effect of tobacco smoke exposure on either biomarker in any group. Levels of both protein carbonyls and 15-F(2t)-IsoP in cord blood significantly correlated with those in maternal plasma (p<0.001). 8-oxodG levels positively correlated with plasma carbonyls in cord plasma, as well as with cotinine levels (marker of tobacco smoke exposure) in maternal plasma. 8-oxodG levels also correlated with bulky DNA adducts in lymphocyte DNA of newborns and mothers and with PAH-DNA adducts in the placenta. Our results showed higher lipid peroxidation in newborns than in mothers, close correlation of analyzed oxidative stress markers between newborns and mothers, and a relationship between oxidative stress and induction of DNA adducts.

Biomarkers of exposure to tobacco smoke and environmental pollutants in mothers and their transplacental transfer to the foetus. Part I: bulky DNA adducts.

(32)P-postlabelling and PAH-ELISA using the antiserum #29 were employed to analyze DNA adducts in venous and umbilical cord blood and the placenta of 79 mothers giving birth to 80 living babies in Prague (Czech Republic). Ambient air exposure was measured by stationary measurements of basic air pollutants (PM2.5, c-PAHs) during the entire pregnancy. Tobacco smoke exposure was assessed by questionnaire data and by plasma cotinine levels. The total DNA adduct levels in the lymphocytes of mothers and newborns were elevated by 30-40% (p<0.001) compared with the placenta. B[a]P-like DNA adduct (adduct with the identical chromatographic mobility on TLC as major BPDE derived DNA adduct) levels were elevated in the blood of mothers compared with the placenta and the blood of newborns (p<0.05 and p<0.01). In tobacco smoke-exposed mothers, higher DNA adduct levels in the blood of mothers and newborns compared with the placenta were found (p<0.001), whereas the total and B[a]P-like adduct levels were comparable in the blood of mothers and newborns. B[a]P-like adducts were elevated in the blood of mothers unexposed to tobacco smoke compared with that of corresponding newborns and the placenta (p<0.01). Total and B[a]P-like DNA adducts were increased in the placenta of tobacco smoke-exposed compared with unexposed mothers (p<0.001 and p<0.01). In lymphocytes of tobacco smoke-exposed mothers, the comparison of total adduct levels (1.18+/-0.67 vs. 0.92+/-0.28) and B[a]P-like DNA adducts (0.22+/-0.12 adducts/10(8) nucleotides vs. 0.15+/-0.06 adducts/10(8) nucleotides) with newborns indicated a 30-40% increase of adducts in mothers. Almost equal PAH-DNA adduct levels were detected by anti-BPDE-DNA ELISA in the placenta of tobacco smoke-exposed and -unexposed mothers. Our results suggest a protective effect of the placental barrier against the genotoxic effect of some tobacco smoke components between the circulation of mother and child. We found a correlation between adduct levels in the blood of mothers and newborns.