Human population studies with the exfoliated buccal micronucleus assay: statistical and epidemiological issues.

Objectives: Micronucleus (MN) assay in buccal exfoliated cells is a minimally invasive method for monitoring genetic damage in human populations. Statistical and epidemiological issues related to the design and analysis of studies based on this biomarker are addressed.

Methods: A systematic review of recent literature on the buccal MN assay has been carried out to provide a state-of-the-art evaluation of how critical topics such as control for confounding, sample size and statistical power, number of cells scored, endpoint selection, and statistical modelling, are considered.

State of the art survey of the buccal micronucleus assay--a first stage in the HUMN(XL) project initiative.

The study of DNA damage in exfoliated buccal cells is a minimally invasive method for monitoring populations for exposure to genotoxic agents. The presence of micronuclei (MN) and other nuclear anomalies within these cells has been shown to be associated with genetic defects in genome maintenance, accelerated ageing, genotoxic damage and some degenerative diseases. To identify important information gaps regarding these biomarkers, a new initiative was launched within the framework of the HUman MicroNucleus (HUMN) collaborative programme, the HUMN(XL) project ('XL' designating eXfoLiated cell).

A novel Bim-BH3-derived Bcl-XL inhibitor: biochemical characterization, in vitro, in vivo and ex-vivo anti-leukemic activity.

BH3-only members of the Bcl-2 family exert a fundamental role in apoptosis induction. This work focuses on the development of a novel peptidic molecule based on the BH3 domain of Bim. The antiapoptotic molecule Bcl-X(L), involved in cancer development/progression and tumour resistance to cytotoxic drugs, is a target for Bim.

Internalization via Antennapedia protein transduction domain of an scFv antibody toward c-Myc protein.

We constructed a single-chain variable fragment miniantibody (G11-scFv) directed toward the transactivation domain of c-Myc, which is fused with the internalization domain Int of Antennapedia at its carboxyl terminus (a cargo-carrier construct). In ELISA experiments, an EC(50) for binding saturation was achieved at concentrations of G11-scFv-Int(-) of approximately 10(-8) M. Internalization of a fluoresceinated Fl-G11-scFv-Int(+) construct was observed in intact human cultured cells with confocal microscopy.