Procarbazine is a potent mutagen at the heterozygous thymidine kinase (tk +/-) locus of mouse lymphoma assay.
Procarbazine (Natulan) is a potent inducer of gene mutations at the heterozygous tk +/- locus in L5178Y mouse lymphoma cells in the presence of Aroclor-induced rat liver S9 metabolic activation (approximately 10(-3) mutant frequency at 10 micrograms/ml) while exerting a far weaker effect in the absence of S9. This mutagenicity is fairly robust with respect to the quantitative composition of the S9 mix and to variations in mouse lymphoma assay protocols (soft agar cloning versus 'microwell' assays). The high proportion of small colony tk -/- mutants induced by procarbazine together with the far weaker mutagenic response at the hemizygous hgprt locus in these same cells is interpreted in terms of a chromosomal or multi-gene mutational mechanism. Although procarbazine is clastogenic in vivo, it does not appear to be so under standard protocols using cultured human lymphocytes (+/- S9). It is not yet clear why this should be so, especially in light of its apparent clastogenicity in mouse lymphoma cells.
Clive
D
D
Genetic Toxicology Laboratory, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Turner
N
N
Krehl
R
R
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D006579:Heterozygote; D007940:Leukemia L5178 / Q000201:enzymology*; D007942:Leukemia, Experimental / Q000201:enzymology*; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D011344:Procarbazine / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics*
D001140:Aroclors; D009153:Mutagens; D011344:Procarbazine; D013937:Thymidine Kinase