Metabolic activation and covalent binding to nucleic acids of pentachloroethane as short-term test of genotoxicity.
The in vivo covalent binding of 14C-pentachloroethane to DNA, RNA and proteins of rats and mouse organs was detected 22 hr after i.p. injection. The covalent binding index, calculated on the liver labeling was comparable to those of compounds considered as weak-moderate initiators. Like other haloalkanes, 14C-pentachloroethane was bioactivated in in vitro cell-free system by both microsomal and cytosolic enzymatic fractions from mouse and rat organs to react covalently with DNA and other macromolecules. The binding extents obtained from in vitro incubation and the binding values detected after in vivo administration of labeled pentachloroethane were comparable each other and showed a high correlation with oncogenic potency index of this compound. This result confirms the efficiency of in vitro binding as short-term test of genotoxicity prediction.
Turina
M P
MP
Centro Interuniversitario per la Ricerca sul Cancro, Università di Bologna, Italy.
Colacci
A
A
Grilli
S
S
Mazzullo
M
M
Prodi
G
G
Lattanzi
G
G
Bonora
B
B
Bartoli
S
S
Guidotti
L
L
D000818:Animals; D001711:Biotransformation; D004247:DNA / Q000378:metabolism*; D004980:Ethane / Q000031:analogs & derivatives* / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D004247:DNA; D004980:Ethane; C016036:pentachloroethane