Association between maternal diet, smoking, and the placenta MTHFR 677C/T genotype and global placental DNA methylation.

INTRODUCTION: The placenta provides nutrients to the fetus, and it has protective effects against harmful substances. Unhealthy maternal diets and toxic agents might increase free radical (FR) production. Elevated FR levels are associated with a high risk of oxidative stress, which may cause DNA damage. DNA might be oxidized in the placenta, occasionally affecting its methylation profile due to 8-hidroxy-2'-deoxyguanosine formation. METHODS: This study assessed 130 mothers and their children. The maternal's nutritional patterns were determined using the Food Frequency Questionnaire. Information on smoking and alcohol consumption was collected during the medical examination. Data on placental DNA were obtained to determine the MTHFR 677C/T genotype and the proportion of placental DNA methylation (pDNAm). RESULTS: Consumption of vitamins and folic acid was above 85%. The pDNAm was found to be correlated with gestational age and coffee intake. Mothers with a smoking history had a low pDNAm. Placentas with the TT genotype had a higher but not significant pDNAm. In the placentas with the CC/CT genotype, the pDNAm was positively associated with carbohydrate and biotin intake. However, the TT genotype was negatively associated with folate and vegetable intake. DISCUSSION: The pDNAm was positively associated with coffee intake, but not with macro-, and micronutrient intake. However, it was negatively associated with cigarette smoking. The placentas with the CC/CT genotype had a lower pDNAm than those with the TT genotype. In the placentas with the CC/CT or TT genotype, methylation was positively, and negatively associated with micro- or macronutrients, respectively.

Polyethylene Incorporating Diels-Alder Comonomers: A "Trojan Horse" Strategy for Chemically Recyclable Polyolefins.

Polyolefins with periodic unsaturation in the backbone chain are sought after for synthesizing chemically recyclable polymers or telechelic polyolefin macromonomers. Here we introduce a bottom-up synthesis of unsaturated high-density polyethylene (HDPE) via copolymerization of ethylene with dimethyl 7-oxabicyclo[2.2.1]hepta-2,5-diene-3,5-dicarboxylate followed by post-polymerization retro-Diels-Alder to unveil hidden double bonds in the polymer backbone. The incorporation of this "Trojan Horse" comonomer was varied and a series of unsaturated HDPE polymers with block lengths of 1.2, 1.9, and 3.5 kDa between double bonds was synthesized. Cross metathesis of unsaturated HDPE samples with 2-hydroxyethyl acrylate yielded telechelic ester terminated PE macromonomers suitable for the preparation of ester-linked PE. These materials were depolymerized and repolymerized, making them suitable candidates for chemical recycling. The ester-linked PE displayed thermal and mechanical properties comparable to commercial HDPE.

Catalytic Chemical Recycling of Post-Consumer Polyethylene.

Among commercial plastics, polyolefins are the most widely produced worldwide but have limited recyclability. Here, we report a chemical recycling route for the conversion of post-consumer high-density polyethylene (HDPE) into telechelic macromonomers suitable for circular reprocessing. Unsaturation was introduced into HDPE by catalytic dehydrogenation using an Ir-POCOP catalyst without an alkene acceptor. Cross-metathesis with 2-hydroxyethyl acrylate followed by hydrogenation transformed the partially unsaturated HDPE into telechelic macromonomers. The direct repolymerization of the macromonomers gave a brittle material due to the low overall weight-average molecular weight. Aminolysis of telechelic macromonomers with a small amount of diethanolamine increased the overall functionality. The resulting macromonomers were repolymerized through transesterification to generate a polymer with comparable mechanical properties to the starting post-consumer HDPE waste. Depolymerization of the repolymerized material catalyzed by an organic base regenerated the telechelic macromonomers, thereby allowing waste polyethylene materials to enter a chemical recycling pathway.

Maternal obesity increases oxidative stress in the newborn.

OBJECTIVE: Obesity before pregnancy is associated with a greater risk for the offspring to develop obesity and diabetes in childhood and adulthood. The aim of the present study was to determine the association between maternal overweight or obesity before pregnancy and newborn oxidative stress (OS). METHODS: Seventy-two mother-child pairs were divided according to the pre-gestational body mass index (BMI) of the mothers as follows: eutrophic (n = 21), overweight (n = 32), and obese (n = 19). Malondialdehyde (MDA) and nitric oxide (NO) were measured in the plasma of a blood sample from the newborn's umbilical cord. RESULTS: The MDA levels of newborns increased with maternal BMI (P = 0.001), as did the levels of NO (P = 0.019). There was a direct correlation between MDA and NO levels in each of the three groups (eutrophic: R(2) = 0.59, P < 0.001; overweight: R(2) = 0.45, P < 0.001; and obese: R(2) = 0.26, P = 0.024). CONCLUSIONS: Maternal overweight and obesity before pregnancy are associated with increased OS in the offspring.

Differential activation of p53 by the various adducts of mitomycin C.

Mitomycin C (MC) is a cytotoxic chemotherapeutic agent that causes DNA damage in the form of DNA cross-links as well as a variety of DNA monoadducts and is known to induce p53. The various DNA adducts formed upon treatment of mouse mammary tumor cells with MC as well as 10-decarbamoyl MC (DMC) and 2,7-diaminomitosene (2,7-DAM), the major MC metabolite, have been elucidated. The cytotoxicity of DMC parallels closely that of MC in a number of rodent cell lines tested, whereas 2,7-DAM is relatively noncytotoxic. In this study, we investigate the ability of MC, DMC, and 2,7-DAM to activate p53 at equidose concentrations by treating tissue culture cell lines with the three mitomycins. Whereas MC and DMC induced p53 protein levels and increased the levels of p21 and Gadd45 mRNA, 2,7-DAM did not. Furthermore, MC and DMC, but not 2,7-DAM, were able to induce apoptosis efficiently in ML-1 cells. Therefore the 2,7-DAM monoadducts were unable to activate the p53 pathway. Interestingly, DMC was able to initiate apoptosis via a p53-independent pathway whereas MC was not. This is the first finding that adducts of a multiadduct type DNA-damaging agent are differentially recognized by DNA damage sensor pathways.