Light and electron microscopic study of fetal lung following maternal exposure to methylmercuric chloride

Varying dose levels of methylmercuric chloride (MMC), 1000 ppm (5 mg through 15 mglkg of body weight), were administered via an intragastric tube to pregnant ICR SwissIWebster mice on day 9 of gestation. The animals were killed on gestational day 18 and the fetuses removed. Fetal lung sections were processed for light and electron microscopy. A group of animals treated with physiological saline in a similar mannner served as the controls. The fetal lungs from treated animals were hypoplastic and retarded in development. The severity of pulmonary changes increased with the dose-levels of MMC. Vacuolation and lysis of mitochondria were seen in fetal lungs. Mitochondrial damage increased in severity with doselevel of methylmercuric chloride

Cytostatic action of methylmercuric chloride on mammalian duodenal cells

Adult male mice of the ICRISwiss Webster strain received a single intragastric administration of methylmercuric chloride 1,000 ppm, at dose levels of 5,10,15,20,25 and 30 mglkg of body weight. The animals were killed six hours later. Tissue samples from the duodenum were fixed in 10% neutral buffered formalin for light microscopy. Chromosome clumping was observed in dividing cells at all dose levels, resembling a C-mitotic effect. It would lead to reduced mitotic cell formation on account of the subsequent lysis of the arrested metaphases. The cytostatic effect was brought about by the inactivation of the microtubule spindle fiber polymerization mechanism induced by methylmercuric chloride. There was a direct positive correlation between the varying dose levels of methylmercury and the proportion of cells arrested in metaphase in the crypts of the duodenum

SIRT2: Tumour suppressor or tumour promoter in operable breast cancer?

Purpose Sirtuins comprise a family of genes involved in cellular stress, survival and damage responses. They have been implicated in a range of diseases including cancer, with most information pertaining to their function in tumourigenesis being derived from in vitro studies, or model organisms. Their putative roles as tumour suppressors or tumour promoters remain to be validated in vivo. Little is known about their role in breast tumourigenesis. We sought to evaluate the seven sirtuin family members (SIRT1–7) in a human breast cancer cohort, in relation to clinico-pathological features and outcome of the disease.<p></p> Materials and methods Immunohistochemical analysis of SIRT1–7 protein levels was undertaken in 392 oestrogen receptor (ER+ve) and 153 ER−ve breast tumour samples. SIRT1–7 transcriptional levels were assessed in normal (n = 25), non-malignant (n = 73) and malignant (n = 70) breast tissue using Relative Quantitative Real Time PCR. Statistical analyses determined if SIRT1–7 transcription or protein expression was associated with clinical parameters or outcome.<p></p> Results In ER−ve tumours, high protein levels of nuclear SIRT2 were associated with reduced time to recurrence and disease-specific death. This association was only observed in Grade 3 tumours. In the ER+ve cohort, high SIRT2 nuclear levels were associated with shorter disease-free survival and time to recurrence whilst on Tamoxifen, in patients with Grade 3 tumours. Conversely, in Grade 2 tumours, high SIRT2 levels were associated with increased time to recurrence.<p></p> Conclusions Our data suggest that SIRT2 is the sirtuin predominantly involved in breast tumourigenesis and prognosis. It indicates that SIRT2 acts as a tumour suppressor or tumour promoter dependent upon breast tumour grade.<p></p&gt