Germ cell mutagenesis in lambda lacZ transgenic mice treated with ethylnitrosourea; comparison with specific-locus...

Area of Science:

• Toxicology
• Genetics
• Mammalian models

Background:

• Germ cell mutagenesis is crucial for understanding heritable genetic damage.
• The specific-locus test is a standard method, but transgenic models offer complementary approaches.
• Validating transgenic models against established methods is essential for reliable data.

Purpose of the Study:

• To compare germ cell mutagenesis data from lambda lacZ transgenic mice with specific-locus test data.
• To validate the utility of the lambda lacZ transgenic mouse model for mutagenesis studies.
• To investigate ethylnitrosourea (ENU)-induced mutagenesis across different spermatogenesis stages.

Main Methods:

• Male lambda lacZ transgenic mice were treated with ethylnitrosourea (ENU).
• Mutant frequency (MF) was assessed at various time points post-treatment (0.1, 7, 50, 100 days).
• DNA adduct levels (O6-ethylguanine) were measured to assess spermatogenesis delay.

Main Results:

• ENU (150 mg/kg) significantly increased MF (9-fold) only in stem cells at 100 days post-treatment.
• No significant MF increase was observed in post-stem cells at earlier time points (0.1 and 7 days).
• A dose-response study revealed a mutation induction threshold in stem cells, consistent with specific-locus test data.

Conclusions:

• Lambda lacZ transgenic mice are a suitable model for studying germ cell mutagenesis, particularly in spermatogonial stem cells.
• The model's data aligns with specific-locus test findings, supporting its validation.
• Spermatogenesis delay was observed, influencing the timing of mutation detection.