Strange goings-on in the mouse germ line.
It is a conventional paradigm that mutagens lead to changes in nucleotide sequence when the cell attempts to repair or replicate lesions in DNA (such as adducts or strand breaks) that have been produced by the mutagens or their metabolites. The resulting changes are located at (or very near) the sites of the initial damage. This is the underlying theory behind mutational spectra work, but how general is it in vivo? Work with ionising radiation has shown that there are interesting things going on in the mouse germ line that do not fall within the conventional paradigm. Mutations occur at certain sites remote from initial DNA damage and in greater than expected number. Bryn Bridges discusses some recent papers on mutational changes in the germ line of mice following exposure to chemical mutagens that suggest that such phenomena may not be confined to radiation.
Bridges
Bryn A
BA
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK. b.a.bridgers@sussex.ac.uk
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea / Q000633:toxicity; D005047:Etoposide / Q000633:toxicity; D005854:Germ Cells / Q000187:drug effects* / Q000528:radiation effects; D018095:Germ-Line Mutation / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008297:Male; D008698:Mesylates / Q000633:toxicity; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000633:toxicity; D011839:Radiation, Ionizing; D013093:Spermatogonia / Q000187:drug effects* / Q000528:radiation effects; D020080:Tandem Repeat Sequences / Q000187:drug effects
D000477:Alkylating Agents; D008698:Mesylates; D009153:Mutagens; D019384:Nucleic Acid Synthesis Inhibitors; D005047:Etoposide; D005038:Ethylnitrosourea; C002531:isopropylmethanesulfonate