INDUCTION OF SPECIFIC-LOCUS AND DOMINANT LETHAL MUTATIONS IN MALE-MICE BY 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA (BCNU) AND 1-(2-CHLOROETHYL)-3-CYCLOHEXYL-1-NITROSOUREA (CCNU)
Uh. Ehling et al., INDUCTION OF SPECIFIC-LOCUS AND DOMINANT LETHAL MUTATIONS IN MALE-MICE BY 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA (BCNU) AND 1-(2-CHLOROETHYL)-3-CYCLOHEXYL-1-NITROSOUREA (CCNU), Mutation research, 379(2), 1997, pp. 219-231
1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-cy
clohexyl-1-nitrosourea (CCNU) induced dominant lethal and specific-loc
us mutations in male mice. For both compounds the germ cell stage sens
itive to the induction of dominant lethal mutations was dose dependent
. A dose of 5 mg BCNU per kg b.wt. induced dominant lethal mutations p
rimarily in spermatocytes, whereas higher doses of BCNU induced domina
nt lethals in spermatids and spermatocytes. Following doses of 5 and 1
0 mg CCNU per kg b.wt. dominant lethals were induced in spermatids and
spermatocytes similar to the results for higher doses of BCNU. Higher
dose exposure to BCNU and CCNU was associated with dominant lethals e
xpressed as pre-implantation loss (reduction in total number of implan
ts). In addition, higher doses of CCNU showed a cytotoxic effect in di
fferentiating spermatogonia. Both compounds induced specific-locus mut
ations in post-spermatogonial germ cell stages of mice. However, CCNU
increased also the specific-locus mutation frequency in spermatogonia
in two out of three experiments. We conclude in analogy with criteria
developed by IARC, that BCNU and CCNU are potential human mutagens. (C
) 1997 Elsevier Science B.V.