Studies on chemical induction of chromosomal aberrations in postcopulation germ cells and zygotes of female mice. I. Comparative studies on the frequency of first-cleavage chromosomal aberrations and dominant-lethal mutations.

ABSTRACT There is a close relationship between the rates at which dominant lethal mutations and heritable translocations are induced by ethyl methanesulfonate (EMS) or triethylenemelamine (TEM) in male postmeiotic germ cells. This relationship does not hold for isopropyl methanesulfonate (IMS), which induced only negligible frequencies of heritable translocations at doses that induced high levels of dominant lethal mutations. Nor does IMS behave like EMS and TEM in the degree to which eggs of different stocks of females repair premutational lesions that are carried in the sperm—large differences between stocks for IMS treatment and small differences for EMS or TEM treatment. These dissimilarities between IMS and the other two alkylating chemicals are postulated to be attributable to differences in the types of lesions present at the time of repair activity and to whether or not chromosomal aberrations are already fixed prior to postfertilization pronuclear DNA synthesis.

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Chemical induction of presumed dominant-lethal mutations in postcopulation germ cells of mice. I. Relative sensitivity between pre- and postcopulation germ cells to isopropyl methanesulfonate

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/0027-5107(75)90006-8 ◽

1975 ◽

Vol 30 (3) ◽

pp. 355-363 ◽

Cited By ~ 4

Author(s):

Kurt E. Suter

Keyword(s):

Germ Cells ◽

Relative Sensitivity ◽

Chemical Induction ◽

Lethal Mutations ◽

Dominant Lethal ◽

Dominant Lethal Mutations

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Chemical Induction of Dominant Lethal Mutations in Mammals

Perspectives in Basic and Applied Toxicology ◽

10.1016/b978-0-7236-0837-0.50011-5 ◽

1988 ◽

pp. 199-205

Author(s):

A. Philip Leber

Keyword(s):

Chemical Induction ◽

Lethal Mutations ◽

Dominant Lethal ◽

Dominant Lethal Mutations

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Induction of specific-locus and dominant lethal mutations in male mice by ifosfamide (Holoxan)

Genetics Research ◽

10.1017/s0016672398003413 ◽

1998 ◽

Vol 72 (3) ◽

pp. 177-183 ◽

Cited By ~ 1

Author(s):

U. H. EHLING ◽

J. FAVOR ◽

A. NEUHÄUSER-KLAUS ◽

I.-D. ADLER

Keyword(s):

Germ Cell ◽

Germ Cells ◽

Genetic Risk ◽

Male Mice ◽

Induced Mutations ◽

Lethal Mutations ◽

Dominant Lethal ◽

Cell Specificity ◽

Dominant Lethal Mutations ◽

Specific Locus

Ifosfamide induced dominant lethal mutations in spermatozoa of mice at doses of 200 and 300 mg/kg and in spermatids and spermatocytes at 600 mg/kg. The highest dose also induced specific-locus mutations in post-spermatogonial germ-cell stages of mice but not in spermatogonial stem cells. The nature of the induced mutations suggests they are intergenic. The spermatogenic specificity of ifosfamide in mouse germ cells is similar to that of the structurally related cytostatic drugs cyclophosphamide and trofosfamide. Due to the post-spermatogonial germ cell specificity of ifosfamide, the genetic risk is limited to a few weeks after exposure.

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