Assessment of the three-test genetic toxicology battery for groundwater metabolites.

The two-test in vitro battery for genotoxicity testing (Ames and micronucleus) has in the majority of cases replaced the three-test battery (as two-test plus mammalian cell gene mutation assay) for the routine testing of chemicals, pharmaceuticals, cosmetics, and agrochemical metabolites originating from food and feed as well as from water treatment. The guidance for testing agrochemical groundwater metabolites, however, still relies on the three-test battery. Data collated in this study from 18 plant protection and related materials highlights the disparity between the often negative Ames and in vitro chromosome aberration data and frequently positive in vitro mammalian cell gene mutation assays.

Ribozyme-mediated inhibition of PKCalpha sensitizes androgen-independent human prostate cancer cells to cisplatin-induced apoptosis.

Background: Therapeutic strategies to target the molecular basis of hormone and drug resistance of prostate cancer cells are needed. Since protein kinase Calpha (PKCalpha) is thought to have a role in the development of the androgen-independent phenotype of prostate cancer cells and in apoptosis suppression, the objective of the present study was to test whether specific inhibition of PKCalpha by a hammerhead ribozyme was able to sensitize androgen-independent prostate cancer cells the effects of apoptosis-inducing anticancer drugs.

Methods: An active ribozyme (PKCalphaRZ) targeting codon 4 in human PKCalpha mRNA was synthesized by in vitro transcription.

p16(INK4A) Hypermethylation detected by fluorescent methylation-specific PCR in plasmas from non-small cell lung cancer.

Purpose: The p16(INK4A) tumor suppressor gene is inactivated in many solid tumors, including non-small cell lung cancers (NSCLCs), through promoter hypermethylation. Presence of p16(INK4A) hypermethylation in precursor lesions of NSCLC and in body fluids of individuals at risk makes it a potential candidate for early disease detection. However, the current low sensitivity of p16(INK4A) hypermethylation detection in plasma limits its consideration in a diagnostic grid.