Evaluation of the yeast DEL assay with 10 compounds selected by the International Program on Chemical Safety for the evaluation of short-term tests for carcinogens

Carcinogens induce reversion of the mouse pink-eyed unstable mutation

“…Preliminary data with Salmonella-negative carcinogens, such as carbon tetrachloride and peroxisome proliferators, yielded negative results with the transgenic mouse mutation assays (47,48), which has led to the general belief that these chemicals may be undetectable with the transgenic mouse mutation assays (43). Because Salmonella-negative as well as Salmonellapositive carcinogens have been shown to induce DEL recombination in yeast (12)(13)(14) and in human cells (17), it was important to determine the effect of selected examples of both classes of carcinogens on DEL recombination in our in vivo mouse model. The present paper shows that DEL recombination in vivo in the mouse is, in fact, inducible by examples of both classes of carcinogens.…”

“…Total RNA was isolated using guanidinium thiocyanate-phenol extraction (40). The first-strand cDNA synthesis was performed using the SuperScript II reverse transcriptase preamplification system and oligo(dT) [12][13][14][15][16][17][18] (GIBCO͞BRL). The first-strand cDNA synthesis reaction contained 5 g total RNA͞1 ϫ PCR buffer (GIBCO͞BRL)͞2.5 mM MgCl 2 ͞0.5 mM dNTP mix͞10 nM DTT.…”

“…DEL recombination is inducible by a wide variety of carcinogens, including carcinogens that are negative in most other shortterm tests (12)(13)(14)(15). In addition, deletion events of one copy of a partial duplication of the hprt gene are inducible by several carcinogens in CHO cells (16) and in human cells (17).…”

“…ENU gives a very weak response in the standard Salmonella assay (36,37). Among these agents, ␥-rays, EMS, MMS, and benzene have been tested with the yeast DEL assay and give positive responses (12)(13)(14). In addition, ␥-rays, MMS, and benzene induce deletions in human cells (17).…”

Carcinogenicity and Other Health Effects of Acrylonitrile with Reference to Occupational Exposure Limit.

“…Induction of mutation was also reported in Escherichia coli by Venitt et al (1977) 41) , and in yeast by Rizzi et al (1983) 55) and Carls and Schiestl (1994) 56) . In experiments using cultured mammalian cells, the following positive responses were observed: transformation of Syrian golden hamster embryo cells (Parent and Casto, 1979) 57) ; induction of repairing synthesis in HeLa cells (Rizzi et al, 1983) 55) ; sister-chromatid exchange in Chinese hamster ovary cells (CHO) (Ved-Brad and Williams, 1982) 58) ; and in vitro transformation of C3H/10T1/2 cells (embryo cells from C3H mice) and fibroblasts from NIH/3T3 mice (Banerjee and Segal, 1986) 59) .…”