Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations.
Six monofunctional alkylating agents, trenimon, cyclophosphamide, and isoniazid were proven for transplacental cytogenetic activity in mouse embryos at day 10 of gestational age under the same conditions as used in the mammalian spot test. With the exception of isoniazid, all compounds led to an increase in the aberration frequencies in embryonal cells. The results were statistically not significant in the case of EMS, while all other chemicals showed a dose-dependent clastogenic activity. After treatment with monofunctional alkylants, chromatid breaks were dominating, while polyfunctional compounds also produced chromatid exchanges, especially in the case of trenimon. ENU and DMS showed a very early aberration maximum 6 hr after injection. For both compounds, very similar dose-response curves were found for induction of chromatid breaks in the dose range 10-75 mg/kg. There is no correlation between the Swain-Scott factors of monofunctional alkylants and their ability to induce chromosomal damage when compared in terms of pharmacological doses. A quantitative comparison of data found in the cytogenetic test in embryonal cells with those obtained in the mammalian spot test led to the conclusion that chromosomal mutations are of minor relevancy for the expression of recessive alleles in heterozygous mouse embryos. With this respect, the mammalian spot test must be considered as an in vivo test for the detection of gene mutations in somatic cells of the mouse.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002869:Chromosome Aberrations; D003520:Cyclophosphamide / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D005865:Gestational Age; D007538:Isoniazid / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D013329:Structure-Activity Relationship; D013463:Sulfuric Acid Esters / Q000633:toxicity; D014228:Triaziquone / Q000633:toxicity
D000477:Alkylating Agents; D013463:Sulfuric Acid Esters; D003520:Cyclophosphamide; D005020:Ethyl Methanesulfonate; D014228:Triaziquone; C007482:dimethyl sulfate; C011612:diethyl sulfate; D005038:Ethylnitrosourea; D007538:Isoniazid