Species differences in mutagenicity testing. II. Sister-chromatid exchange and micronucleus induction in rats, mice and Chinese hamsters treated with cyclophosphamide

Abstract

Comparative investigations of sister-chromatid exchange (SCE) and micronucleus induction in the bone marrow of rats, mice and Chinese hamsters with the cytostatic alkylating mutagen cyclophosphamide (CP) revealed remarkable species differences in their mutagenic responses. With both test systems the sensitivities of the three species can be ranked into the order rat greater than mouse greater than Chinese hamster. More explicit results were obtained with the SCE test than with the micronucleus test within the same dose range. This may be due to the influence of species-related differences in the cytotoxic response to CP in the micronucleus test. These results show that clearly different mutagenic responses in different test species may be obtained in standard assays even with a compound which is metabolized in a very similar manner in all animal species.

Cyclophosphamide cystitis in mice: Behavioural characterisation and correlation with bladder inflammation

“…The difference in the dose required to evoke significant changes in behaviour and bladder inflammation in mice (present study) compared to rats (Lantéri-Minet et al, 1995) may be explained by differences in the metabolism of cyclophosphamide, in the pharmacokinetics of the parent compound or of the toxic metabolites, or in the sensitivity of the bladder to the toxins. The metabolism of cyclophosphamide appears to be very similar in all species (Madle et al, 1986). The pharmacokinetics of the parent compound, and the tissue distribution of the toxic metabolities vary somewhat between species, and even between different strains of mice (Madle et al, 1986;Kanekal et al, 1992), which may contribute to the higher dose required to produce significant effects in mice.…”

Micronucleus formation induced by the combination of low doses of X-rays and antineoplastic drugs in bone marrow of male mice

“…MMC is well known to induce micronuclei in polychromatic erythrocytes in various mouse strains [4,[11][12][13]. CP is a mutagen in the chromosome aberration test, in the sister chromatid exchange and micronucleus test in vivo and in vitro [14][15][16][17][18][19].…”

Cytogenetic Monitoring of Pesticide Sprayers

“…Comparing SCE frequencies and incidence of chromosomal aberrations, as well as yield of micronuclei, it was observed that the values differed. This phenomen had already been described (Madle et al, 1986), and it is explained by different mechanisms in the formation of genetic alterations. There was no correlation between SCE frequency and duration of exposure during the heavy spraying period, but a good correlation between incidence of unstable chromosomal aberrations, especially micronuclei, and duration of exposure was found.…”