Chlorambucil effectively induces deletion mutations in mouse germ cells

Journal Article · Mon May 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.10.3704· OSTI ID:5429317

Russell, L B; Hunsicker, P R; Cacheiro, N L.A.; Bangham, J W; Russell, W L; Shelby, M D ^[1]

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1. Oak Ridge National Laboratory, TN (USA)

The chemotherapeutic agent chlorambucil was found to be more effective than x-rays or any chemical investigated to data in inducing high yields of mouse germ-line mutations that appear to be deletions or other structural changes. Induction of mutations involving seven specific loci was studied after exposures of various male germ-cell stages to chlorambucil at 10-25 mg/kg. A total of 60,750 offspring was scored. Mutation rates in spermatogonial stem cells were not significantly increased over control values; this negative result is not attributable to selective elimination of mutant cells. Mutations were, however, clearly induced in treated post-stem-cell stages, among which marked variations in mutational response were found. Maximum yield occurred after exposure of early spermatids, with {approx} 1% of all offspring carrying a specific-locus mutation in the 10 mg/kg group. The stage-response pattern for chlorambucil differs from that of all other chemicals investigated to date in the specific-locus test. Thus far, all but one of the tested mutations induced by chlorambucil in post-stem-cell stages have been proved deletions or other structural changes by genetic, cytogenetic, and/or molecular criteria. Deletion mutations have recently been useful for molecular mapping and for structure-function correlations of genomic regions. For generating presumed large-lesion germline mutations at highest frequencies, chlorambucil may be the mutagen of choice.

• OSTI ID: 5429317
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:10; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CHLORAMBUCIL
BIOLOGICAL EFFECTS
SPERMATOGONIA
MUTAGENESIS
CHEMOTHERAPY
CHROMOSOMAL ABERRATIONS
DOMINANT MUTATIONS
GENE MUTATIONS
LETHAL MUTATIONS
MICE
MUTATION FREQUENCY
SPERMATOGENESIS
STEM CELLS
X RADIATION
AMINES
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
CARBOXYLIC ACIDS
DRUGS
ELECTROMAGNETIC RADIATION
GAMETES
GAMETOGENESIS
GERM CELLS
IONIZING RADIATIONS
MAMMALS
MONOCARBOXYLIC ACIDS
MUTATIONS
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
RADIATIONS
RODENTS
SOMATIC CELLS
THERAPY
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology