Testing of known carcinogens and noncarcinogens in the Syrian hamster embryo (SHE) micronucleus test in vitro; correlations with in vivo micronucleus formation and cell transformation.

Seventy-five chemicals, carcinogens and noncarcinogens, were tested in the SHE (Syrian hamster embryo) micronucleus test in vitro. Substances inducing a reproducible and dose dependent increase in micronucleus frequency were regarded as positive. The acquired data were analyzed for correlations with results obtained from the in vivo mouse bone marrow micronucleus test and from morphological transformation of SHE cells. Out of 48 carcinogens tested 41 (85%) yielded a positive result and out of 17 noncarcinogens all proved negative. For 7 chemicals no carcinogenicity data were available so far; these compounds yielded no response in the mouse bone marrow and in the SHE micronucleus assay. For 3 chemicals only inadequate carcinogenicity data were available. A high degree of concordance with data from the in vivo micronucleus test was found (89%) and the accordance with results from morphological SHE cell transformation was even higher (95%). These findings provide new evidence that the in vitro SHE micronucleus test does in fact represent a short-term test of high predictive value.

Regulatory structures of gene expression, DNA-replication and DNA-rearrangement in macronuclear genes of Stylonychia lemnae, a hypotrichous ciliate.

Seven transcriptionally active macronuclear DNA molecules of Stylonychia lemnae have been analyzed for potential regulatory sequences of gene expression, DNA replication and DNA rearrangement. Transcription initiation is mediated by a canonical TATA-box or by TATA-box-like sequences, and transcription efficiency may be regulated by gene-specific downstream promoter elements (DPE). Putative signals for RNA 3'-formation are represented by noncon-served palindromes located upstream of the mature RNA 3'-termini. Sequences indicating polyadenylation of the mRNA molecules are not detectable. A single palindrome of A- and T-residues is present within the 80 5'-terminal bases of each macronuclear DNA molecule and very likely functions as the replication origin. The 7 DNA molecules consist of several nonconserved inverted and direct repeats (IR, DR) suggested to play a role in DNA rearrangement during macronuclear development.