A method has been developed for the electrophoretic and quantitative analyses of human red cell delta-aminolevulinate dehydrase (ALADH). The enzyme is under the control of an autosomal gene, with two common codominant alleles. ALADH1 and ALADH2, with frequencies of 0.89 and 0.11, respectively, in the Italian population. Mean phenotypic enzyme activities are nearly identical: 52,. 49 and 55 mIU/g Hb for ALADH 1, 2-1 and 2 phenotypes respectively.

The main results of this study are the high incidence of thyroid and pancreatic antibodies, and the possible role of gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features. (Pediatr Res 59: 111-115, 2006)

In this study, the effects induced in mouse liver by repeated oral exposure to furan were investigated. To this aim, the compound was given for 28 days by daily gavage to male B6C3F1 mice at 2, 4, 8 and 15 mg/kg body weight (b.w.)/day. Twenty-four hours after last administration, animals were sacrificed, liver was excised and the following parameters were evaluated: histological alterations, apoptosis, cell proliferation, polyploidy, overall DNA methylation, gene expression and DNA damage by the immunofluorescence detection of foci of phosphorylated histone H2AX (gamma-H2AX) and by alkaline comet assays, using both standard and modified protocols for the detection of DNA cross links. Liver DNA damage by comet assays was also evaluated in mice receiving furan as a single acute oral dose (15, 100 or 250 mg/kg b.w.). Microscopic analysis of liver sections indicated that repeated oral administration of furan was moderately toxic, producing mild histological alterations with necrotic figures, apoptosis and limited regenerative cell proliferation. The flow cytometric analysis of DNA content in single-cell suspensions of liver cells showed a statistically significant increase in polyploid (8N) cells at the highest dose. No treatment-related changes in overall DNA methylation, gamma-H2AX foci, DNA strand breaks and cross links were observed at the end of the 4-week exposure period. However, several genes involved in DNA damage response, beyond stress and liver toxicity, were over-expressed in mice treated with the highest furan dose (15 mg/kg b.w./day). Acute administration of furan induced evident liver toxicity at the highest dose (250 mg/kg b.w.), which was associated with a significant increase of DNA damage in the alkaline comet assay and with a distinct decrease in gamma-ray-induced DNA migration. Overall, the results obtained suggest that the contribution of genotoxicity to the mechanism of furan carcinogenicity in mouse liver should not be dismissed.

Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (P = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and high frequency cells (HFC, above 90 degrees percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.