Paternal exposure to ethylnitrosourea results in transgenerational genomic instability in mice.
Level 5 - mechanism / opinion, no new human data
Non-clinical animal research with no human data
PubMed 18366099 · doi:10.1002/em.20385
What was done
Male mice from two inbred strains (CBA/Ca and BALB/c) were treated with the alkylating agent ethylnitrosourea (ENU). Researchers assessed transgenerational effects by measuring germline mutation rates at two expanded simple tandem repeat (ESTR) loci in the unexposed first-generation (F1) offspring, comparing outcomes across premeiotic and postmeiotic paternal exposure stages, strain backgrounds, and the sex of the F1 offspring.
What was found
Paternal ENU exposure led to statistically significant elevations in mutation rates at two ESTR loci in the F1 germline of both mouse strains. The magnitude of mutation rate elevation in the F1 germline was similar regardless of whether the paternal exposure occurred at premeiotic or postmeiotic stages. Furthermore, within each strain, germline mutation rates were equally elevated in both male and female F1 progeny. The abstract does not provide specific numerical mutation rates, sample sizes, or effect sizes.
Why it matters
This study demonstrates that transgenerational genomic instability is not exclusively induced by ionizing radiation or double-strand breaks, but can also be triggered by alkylating DNA damage via generalized stress responses.
Limits
The findings are derived entirely from an inbred mouse model and may not directly translate to human germline dynamics or transgenerational risks. The abstract omits specific sample sizes (n), dosage regimens, exact mutation frequencies, and confidence intervals, and it evaluates only two ESTR loci rather than genome-wide mutations.
Cited by
- supports Environmental chemical exposures can cause genetic changes that are inherited by successive generations.