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The genotoxicity of diaveridine and trimethoprim.

Abstract：

:We examined the genotoxicity of diaveridine and trimethoprim in the bacterial umu test, the bacterial reverse mutation test, the in vitro chromosome aberration test, the in vivo rodent bone marrow micronucleus test in two species, and the in vivo comet assay in five mouse organs. Both compounds were negative in the umu test (Salmonella typhimurium TA1535/pSK1002) and in the reverse mutation tests (S. typhimurium TA100, TA98, TA97, TA102, and Escherichia coli WP2 uvrA/pKM101) in the presence and absence of S9 mix. Diaveridine induced structural chromosome aberrations in cultured Chinese hamster CHL cells in the absence of a metabolic activation system, but not in the presence of a liver S9 fraction. No clastogenic activity in CHL cells was detected for trimethoprim. Bone marrow micronucleus tests in mice and rats conducted on diaveridine by single- and triple-oral dosing protocols were negative. The comet assay revealed that a single oral administration of diaveridine significantly induced DNA damage in liver, kidney, lung, and spleen cells, but not in bone marrow cells. The significant increase in migration values of DNA was reproducible with dose-response relationship. We suggest that the liver detoxifies the compound before it reaches the bone marrow, and that is why it is negative in the in vivo bone marrow micronucleus test. We concluded that diaveridine is genotoxic to mammalian cells in vitro and in vivo.

journal_name

Environ Toxicol Pharmacol

journal_title

Environmental toxicology and pharmacology

authors

Ono T,Sekiya T,Takahashi Y,Sasaki YF,Izumiyama F,Nishidate E,Tsuda S,Ohta T

doi

10.1016/s1382-6689(97)00026-4

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

297-306

issue

4

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(97)00026-4

journal_volume

3

pub_type

杂志文章

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