Drug-induced protoporphyria in beagle dogs.

As part of regulatory safety testing program, a 13-week oral toxicity study with a new antipsychotic drug candidate was performed in beagle dogs. During this study, dark red/brown feces were recorded in treated dogs and increases in liver parameters (alanine aminotransferase, alkaline phosphatase, bilirubin) were measured biochemically. At the end of the study, livers of high-dose (50 mg/kg) animals were (mottled) dark brown, sometimes with pale foci.

Evaluation of the database on mutant frequencies and DNA sequence alterations of vermilion mutations induced in germ cells of Drosophila shows the importance of a neutral mutation detection system.

The vermilion gene in Drosophila has extensively been used for the molecular analysis of mutations induced by chemicals in germ cells in vivo. The gene is located on the X-chromosome and is a useful target for the study of mutagenesis since all types of mutations are generated. We have critically evaluated this system with respect to sensitivity for mutation induction and selectivity for different types of mutations, using a database of more than 600 vermilion mutants induced in postmeiotic male germ cells by 18 mutagens.

Strand-specific mutation induction by 1,2-dibromomethane at the hypoxanthine-guanine phosphoribosyltransferase locus of Chinese hamster ovary cells.

The nature of mutations induced by 1,2-dibromoethane (DBE) at the hprt (hypoxanthine-guanine phosphoribosyl-transferase) gene was analysed in Chinese hamster ovary (CHO-9) cells. Molecular characterization of 36 hprt mutants at the cDNA level yielded 19 GC-->AT transitions, two AT-->CG transversions, three frameshift mutations, two identical small deletions and 10 exon deletions. Further analysis of the deletion mutants by amplification of specific exons from genomic DNA showed two more GC-->AT transitions at splice sites and an approximately 70 bp deletion.