Time trends in burdens of cadmium, lead, and mercury in the population of northern Sweden.

The time trends of exposure to heavy metals are not adequately known. This is a worldwide problem with regard to the basis for preventive actions and evaluation of their effects. This study addresses time trends for the three toxic elements cadmium (Cd), mercury (Hg), and lead (Pb). Concentrations in erythrocytes (Ery) were determined in a subsample of the population-based MONICA surveys from 1990, 1994, and 1999 in a total of 600 men and women aged 25-74 years. The study took place in the two northernmost counties in Sweden. To assess the effect of changes in the environment, adjustments were made for life-style factors that are determinants of exposure. Annual decreases of 5-6% were seen for Ery-Pb levels (adjusted for age and changes in alcohol intake) and Ery-Hg levels (adjusted for age and changes in fish intake). Ery-Cd levels (adjusted for age) showed a similar significant decrease in smoking men. It is concluded that for Pb and maybe also Hg the actions against pollution during recent decades have caused a rapid decrease of exposure; for Hg the decreased use of dental amalgam may also have had an influence. For Cd, the decline in Ery-Cd was seen only in smokers, indicating that Cd exposure from tobacco has decreased, while other environmental sources of Cd have not changed significantly. To further improve the health status in Sweden, it is important to decrease the pollution of Cd, and actions against smoking in the community are important.

Genetic influences on the retention of inorganic mercury.

Mercury is eliminated as glutathione (GSH) conjugates. GSH production is mediated by glutamyl-cysteine ligase (GCL), and conjugation by glutathione S-transferases (GST). This study tested if polymorphisms in GCL and GST genes modify mercury retention in humans exposed to elemental mercury vapor. Total mercury concentrations in whole blood, plasma and urine, and genotypes for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 309 gold miners, gold buyers and controls. The presence of the GCLM-588T allele was associated with increased blood, plasma and urine mercury levels. These results indicate that genotypes with decreased GSH availability for mercury conjugation affect the metabolism of inorganic mercury.

Polymorphisms in glutathione-related genes affect methylmercury retention.

Methylmercury is eliminated from the human body as glutathione (GSH) conjugates. GSH production is mediated by glutamyl-cysteine ligase (GCL) and conjugation by glutathione S-transferases (GST). In this study, the authors tested whether polymorphisms in GCL and GST genes modify methylmercury retention. Erythrocyte mercury concentration (EryHg), plasma polyunsaturated fatty acids (PPUFA), and genotype for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 365 individuals. A general linear model was developed for analyzing whether genotype modified the regression of EryHg on PPUFA. The presence of one variant allele for either GCLC-129 or GSTP1-114 was associated with higher EryHg and steeper regression slope. No similar trends were shown for GCLM, GSTA1, GSTM1, or GSTT1. These findings indicate that GCLC polymorphisms that affect GSH production also affect methylmercury retention, and that GSTP1 may play a role in conjugating methylmercury with GSH.

Modelling of normal and premalignant oral tissue by using the immortalised cell line, SVpgC2a: a review of the value of the model.

Normal oral keratinocytes (NOKs), and a Simian virus 40 T-antigen-immortalised oral keratinocyte line termed SVpgC2a, were cultured in an effort to model the human oral epithelium in vitro, including normal and dysplastic tissue. Monolayer and organotypic cultures of NOKs and SVpgC2a were successfully established in a standardised serum-free medium with high levels of amino acids, by using regular tissue culture plastic for monolayers and collagen gels containing oral fibroblasts as the base for generating tissue equivalents. NOKs express many characteristics of normal tissue, including those associated with terminal squamous differentiation. After > 150 passages, SVpgC2a cells retained an immortal, nontumourigenic phenotype that, relative to NOKs, was associated with aberrant morphology, enhanced proliferation, deficiency in terminal differentiation, proneness to apoptosis, and variably altered expression of structural epithelial markers. Transcript and protein profiling, as well as activity assays, demonstrated the expression of multiple xenobiotic-metabolising enzymes in SVpgC2a cells, some of which were higher in comparison to NOKs. A generally preserved, or even activated, ability for xenobiotic metabolism in long-term cultures of SVpgC2a cells indicated that this cell line could be useful in safety testing protocols--for example, in the development of consumer products in the oral health care field. However, SVpgC2a cells displayed some features reminiscent of a severe oral dysplasia, implying that this cell line could also to some extent serve as a model of a premalignant oral epithelium.