Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1

Abstract

Three animal species used in in vivo mutagenicity testing--rats, mice and Chinese hamsters--were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE-inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathione conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an "inappropriate" test species may lead to a false negative judgment on the genotoxic potential of a test compound.

Protective effect of sodium selenite on genotoxicity to human whole blood cultures induced by aflatoxin B1

“…It is a cofactor of the enzyme glutathione peroxidase (Leopold, 1976). Again, glutathione conjugates with AFB 1 (Madle et al, 1986). Thus, it could be possible that AFB 1 -induced oxidative damage acted as an intermediate for the genetic damage observed.…”

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

“…474 recommends to use 5 animals per group and both sexes (OECD, 1997), but this study was performed only with male rats. Madle et al observed that AFB1 induced more MN in male rats and mice than in females (Madle et al, 2005) and it is very well known that OTA is more carcinogenic in male rodents than in females (Castegnaro et al, 1998;EFSA, 2006). Therefore, in order to simplify the design of the study which was technically complicated, it was decided to perform the study only in male rats.…”

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

“…The acute toxicity of cyclophosphamide is primarily associated with its genotoxicity Hayashi, 2000). In somatic cells, it provokes gene mutations, chromosomal aberrations, micronuclei and exchanges of sister chromatids in a variety of cell cultures with and without the presence of metabolic activation (Monteith, Vanstone, 1995;Elhajouji et al, 1994;Madle et al, 1986). Cyclophosphamide also damages chromosomes and micronuclei in the hematopoietic system of rats, mice and Chinese hamsters by producing highly reactive carbon ions (Moore et al, 1995).…”