OBJECTIVES: Cytotoxic methacrylate monomers have been identified in aqueous extracts of freshly cured compomers. Some of these compounds, including HEMA and TEGDMA, induce apoptosis and necrosis in vitro. The aim of the present study was to elucidate possible signaling pathways involved in apoptosis following exposure to HEMA or TEGDMA in a salivary gland cell line. METHODS: The cells were exposed to various concentrations of HEMA or TEGDMA. ROS formation was determined by dichlorofluorescein assay. Phosphorylated MAP-kinases ERK1/2, p38 and JNK, as well as specific caspases were identified by Western blotting. Apoptosis was assayed by fluorescence microscopy. RESULTS: HEMA or TEGDMA exposure resulted in ROS formation and concentration-dependent apoptosis as well as phosphorylation of ERK. Phosphorylation of JNK and p38 was induced by HEMA. Selective inhibitors of ERK and JNK modified the apoptotic response after HEMA and TEGDMA exposure, whereas p38 inhibition modified the apoptotic response only after HEMA exposure. Vitamin C reduced HEMA-induced apoptosis. SIGNIFICANCE: ROS formation and differential MAP kinase activation appear to be involved in the apoptotic response following exposure to HEMA and TEGDMA.
Incubation of neutral salt soluble type III pN-collagen with [14C]acetaldehyde in vitro resulted in the formation of spontaneously stable acetaldehyde-protein adducts. This reaction occurred primarily at lysine residues and it was not affected by 0.2-2 mM concentrations of ascorbate but addition of sodiumcyanoborohydride increased the stable adducts by 3-5-fold. When confluent cultures of human skin fibroblasts were incubated with physiologically relevant concentrations of acetaldehyde, it became covalently bound to type III procollagen secreted into the medium. We propose that acetaldehyde binding to collagen fibrils occurs in vivo following chronic alcohol consumption.
The relation between the intake of retinoids, carotenoids, vitamin E, vitamin C, and selenium and the subsequent risk of lung cancer was studied among 4,538 initially cancer-free Finnish men aged 20-69 years. During a follow-up of 20 years beginning in 1966-1972, 117 lung cancer cases were diagnosed. Inverse gradients were observed between the intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers, for whom the age-adjusted relative risks of lung cancer in the lowest tertile of intake compared with that in the highest tertile were 2.5 (p value for trend = 0.04), 3.1 (p = 0.12), and 3.1 (p less than 0.01) for the three intakes, respectively. Adjustment for various potential confounding factors did not materially alter the results, and the associations did not seem to be due to preclinical cancer. In the total cohort, there was an inverse association between intake of margarine and fruits and risk of lung cancer. The relative risk of lung cancer for the lowest compared with the highest tertile of margarine intake was 4.0 (p less than 0.001), and that for fruits was 1.8 (p = 0.01). These associations persisted after adjustment for the micronutrient intakes and were stronger among nonsmokers. The results suggest that carotenoids, vitamin E, and vitamin C may be protective against lung cancer among nonsmokers. Food sources rich in these micronutrients may also have other constituents with independent protective effects against lung cancer.
Comment In: Am J Epidemiol. 1992 Nov 1;136(9):1167-9; author reply 1169-701462977
Maternal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy has been associated with reduced fetal growth. However, the role of diet, the main source of PAH exposure among non-smokers, remains uncertain.
To assess associations between maternal exposure to dietary intake of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy and birth weight, exploring potential effect modification by dietary intakes of vitamins C, E and A, hypothesized to influence PAH metabolism.
This study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Dietary B(a)P and nutrient intakes were estimated based on total consumption obtained from a food frequency questionnaire (FFQ) and estimated based on food composition data. Data on infant birth weight were obtained from the Medical Birth Registry of Norway (MBRN). Multivariate regression was used to assess associations between dietary B(a)P and birth weight, evaluating potential interactions with candidate nutrients.
The multivariate-adjusted coefficient (95%CI) for birth weight associated with maternal energy-adjusted B(a)P intake was -20.5g (-31.1, -10.0) in women in the third compared with the first tertile of B(a)P intake. Results were similar after excluding smokers. Significant interactions were found between elevated intakes of vitamin C (>85mg/day) and dietary B(a)P during pregnancy for birth weight (P