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Embryopathic action of N-nitrosomethylurea in the male mouse manifest in the first generation
1Life Science Laboratory, Teesside Polytechnic, Middlesbrough, Cleveland, U.K.
Abstract:
Offspring from paternal mice treated with N.M.U. (20 mg/kg/i.p.) incurred an increased incidence of pre and post-weaning mortality. Those conceived immediately after treatment presented a high incidence of tumor bearing animals, double that in the concurrent untreated controls. These events are thought to reflect chemical damage to spermatozoa present at the time of treatment. The relatively high incidence of offspring presenting tumours and which were conceived in later weeks suggest impairment of earlier germ cells. Male offspring conceived in weeks 1 to 4 post-treatment produced a significant incidence of T. B. A.s (p less than 0.01, binomial analysis) and developed 5 types of neoplasia not encountered in male controls; the corresponding females presented 9 kinds of tumour which had no counterpart in the control females. Two features presented a significant change from the control (p less than 0.001, binomial analysis): firstly, the number of reticuloses involving all offspring and secondly the incidence of tumours of vascular origin in female offspring overall.
Insights
Paternal exposure to N-methyl-N-nitrosourea (NMU) significantly increased offspring mortality and tumor incidence. NMU-induced germ cell damage in male mice leads to heritable tumors and developmental abnormalities in offspring.
Area of Science:
- Toxicology
- Reproductive Biology
- Oncology
Background:
- Paternal exposure to environmental mutagens can impact offspring health.
- N-methyl-N-nitrosourea (NMU) is a known mutagen with potential reproductive toxicity.
- Understanding the transgenerational effects of mutagens is crucial for public health.
Purpose of the Study:
- To investigate the effects of paternal NMU exposure on offspring mortality and tumor development.
- To identify specific types of neoplasms induced by NMU in offspring.
- To assess the impact of NMU on different germ cell stages.
Main Methods:
- Paternal mice were treated with NMU (20 mg/kg/i.p.).
- Offspring conceived at different time points post-treatment were analyzed for mortality and tumor incidence.
- Statistical analyses (binomial analysis) were used to compare treatment and control groups.
Main Results:
- Offspring from NMU-treated fathers showed increased pre- and post-weaning mortality.
- A high incidence of tumor-bearing offspring was observed, double that of controls.
- Male offspring (conceived weeks 1-4) developed 5 new neoplasia types; females developed 9.
- Significant increases in reticuloses and vascular tumors in female offspring were noted.
Conclusions:
- Paternal NMU exposure causes significant heritable damage to germ cells.
- This damage leads to increased offspring mortality and a wide spectrum of induced neoplasms.
- NMU poses a substantial risk for reproductive and developmental toxicity.