Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.
A combined cytogeneticurine metabolite analysis approach was used to assess potential interactive effects between Fenarimol (FN), a fungicide, and trichloroethylene (TRI), a halogenated solvent. FN was demonstrated to selectively induce P450-2B1 isoforms in different organs of treated mice. Since the rate of metabolism and the stereospecificity of metabolism are dependent on the types and amount of P450s available, FN might drastically alter the metabolic activation of a precarcinogen, such as TRI, and its toxicological consequences. Male CD1 mice were divided into untreated, vehicle control, and experimental groups. Animals of the latter groups were treated ip with 150 mg/kg bw FN in corn oil, 457 mg/kg bw TRI in corn oil, TRI plus FN separated by different time intervals. Bone marrow cells were harvested for determination of micronuclei (MN) frequencies in polychromatic erythrocytes (PCE). The presence of the known metabolite of TRI, trichloroethanol (TCE), was quantitated in collected urine by gas chromatography using an electron-capture detector. Linear regression analysis shows that MN frequency by TRI is correlated with TCE concentration in urine. Observed potentiation of genotoxicity of TRI by FN pretreatment (1 hr before TRI treatment) apparently reflects changes in the spectra of enzymes involved in TRI metabolism, and altered toxicokinetic, as witnessed by the 20% difference in TCE excretion from combined treated mice. However, no increased genetic or metabolic effects were observed when FN was administered 3 hr before TRI. No significant interactive effects were observed at a genetic level when FN was administered 1 hr and 3 hr after TRI whereas a 33 to 47% loss in TCE excretion was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
Hrelia
P
P
Dipartimento di Farmacologia, Università di Bologna, Italy.
Maffei
F
F
Vigagni
F
F
Fimognari
C
C
Flori
P
P
Stanzani
R
R
Cantelli Forti
G
G
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D004347:Drug Interactions; D005659:Fungicides, Industrial / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D011743:Pyrimidines / Q000378:metabolism* / Q000633:toxicity; D013997:Time Factors; D014241:Trichloroethylene / Q000378:metabolism* / Q000633:toxicity / Q000652:urine
D005659:Fungicides, Industrial; D011743:Pyrimidines; D014241:Trichloroethylene; C033789:fenarimol