Induction of dominant lethal mutations by alkylating agents in male mice

An unscheduled DNA synthesis has been clearly demonstrated in meiotic and postmeiotic germ cell stages of the male mouse after in vivo treatment with a 250 mg/kg dose of ethyl methanesulfonate. The germ cell stages showing unscheduled DNA synthesis range from early to middle meiotic prophase stages through early to middle spermatid stages. The initiation of this synthesis, taken to be repair of chemically damaged DNA in these germ cells, is rapid, beginning within 1 hour after the injection of ethyl methanesulfonate. Unscheduled DNA synthesis has not been detected in the most mature germ cell stages, which give rise to dominant lethal mutations, nor does it occur in germ cell stages where protamine has replaced the chromosomal histones.In the study ofchemical mutagenesis in a mammalian testsystem it is of great interest to know if the germ cells are capable of repairing damaged DNA (as well as other molecular targets), and the relationship between such a repair system, if it does exist, and the genetic consequences of such repair. Studies have been performed with a limited number of mammalian cell types (not including germ cells), which demonstrated repair of chemically damaged DNA. See, for example (1-4). However, in vivo repair of germ cell DNA after treatment with chemical agents has not been studied.It is possible to study DNA repair in meiotic and postmeiotic germ cells of male mice by making use of the wellstudied sequence of events that occurs during spermatogenesis and spermiogenesis (5-7). In developing male germ cells the last DNA synthesis takes place during a 14-hr period (7) in preleptotene spermatocytes. After DNA synthesis these spermatocytes continue to develop through a series of germ cell stages for about a 28-30 day period (5, 6) before the spermatids finally leave the testes and enter the caput epididymides. Two to three days later, the developing sperm reach the caudal epididymides, and, in two or three days more, they enter the vasa deferentia. If Recovery of Sperm Heads and DNA. At various times after treatment the animals were killed and the reproductive tracts were sectioned into three parts: the caput epididymides, the caudal epididymides, and the vasa deferentia (refer to Fig. 1). After pooling of the tissues from each region, the sperm heads were recovered by procedures already described (8).

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“…2 is a generalized dominant lethal curve for a 250 mg/kg dose of EMS taken from refs. [9][10][11]. Also shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Unscheduled DNA Synthesis in the Germ Cells of Male Mice Exposed In Vivo to the Chemical Mutagen Ethyl Methanesulfonate

Sega

1974

Proc. Natl. Acad. Sci. U.S.A.

110

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“…Out of monofunctional alkylating agents, ethylation produces greater frequency of sex-linked recessive lethals than methylation (Alderson 1964); and of chromosomal re-arrangements associated with sex-linked recessive lethals in Drosophila (Fahmy and Fahmy 1961). However, greater efficiency of MMS over EMS has been observed for inducing dominant lethals in male mice (Ehling et al 1968); F1 autosomal complete dominants in Drosophila (Fahmy and Fahmy 1961); DNA alkylation of T4 phages (Lawley and Brookes 1963); and for chromosomal breaks and aberrations in Vicia faba (Grover 1969). The effects presently observed clearly indicate superiority of ethylation over methylation for inducing inversions in Drosophila.…”

Section: Discussionmentioning

confidence: 99%

Cytological Effects of Three Alkylating Agents in <i>Drosophila</i>

Parkash

Miglani

1976

CYTOLOGIA

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“…It should be pointed out that whether this response is due to genetic or toxic effects is not known at the present time. A somewhat similar situation seems to be true for IMS in which there are indications that with certain strains of mice females may be more sensitive to induction of dominant lethals than males (7,33).…”

Section: Heritable Reciprocal Translocationsmentioning

confidence: 87%

Evaluation of Chromosome Aberration Effects of Chemicals on Mouse Germ Cells

Generoso¹

1973

Environmental Health Perspectives

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Induction of dominant lethal mutations by alkylating agents in male mice

Cited by 207 publications

References 22 publications

Unscheduled DNA Synthesis in the Germ Cells of Male Mice Exposed In Vivo to the Chemical Mutagen Ethyl Methanesulfonate

Unscheduled DNA Synthesis in the Germ Cells of Male Mice Exposed In Vivo to the Chemical Mutagen Ethyl Methanesulfonate

Cytological Effects of Three Alkylating Agents in <i>Drosophila</i>

Evaluation of Chromosome Aberration Effects of Chemicals on Mouse Germ Cells

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