NanoTIO(2) (UV-Titan) does not induce ESTR mutations in the germline of prenatally exposed female mice.
BACKGROUND
Particulate air pollution has been linked to an increased risk of cardiovascular disease and cancer. Animal studies have shown that inhalation of air particulates induces mutations in the male germline. Expanded simple tandem repeat (ESTR) loci in mice are sensitive markers of mutagenic effects on male germ cells resulting from environmental exposures; however, female germ cells have received little attention. Oocytes may be vulnerable during stages of active cell division (e.g., during fetal development). Accordingly, an increase in germline ESTR mutations in female mice prenatally exposed to radiation has previously been reported. Here we investigate the effects of nanoparticles on the female germline. Since pulmonary exposure to nanosized titanium dioxide (nanoTiO(2)) produces a long-lasting inflammatory response in mice, it was chosen for the present study.


RESULTS
Pregnant C57BL/6 mice were exposed by whole-body inhalation to the nanoTiO(2) UV-Titan L181 (~42.4 mg UV-Titan/m(3)) or filtered clean air on gestation days (GD) 8-18. Female C57BL/6 F1 offspring were raised to maturity and mated with unexposed CBA males. The F2 descendents were collected and ESTR germline mutation rates in this generation were estimated from full pedigrees (mother, father, offspring) of F1 female mice (192 UV-Titan-exposed F2 offspring and 164 F2 controls). ESTR mutation rates of 0.029 (maternal allele) and 0.047 (paternal allele) in UV-Titan-exposed F2 offspring were not statistically different from those of F2 controls: 0.037 (maternal allele) and 0.061 (paternal allele).


CONCLUSIONS
We found no evidence for increased ESTR mutation rates in F1 females exposed in utero to UV-Titan nanoparticles from GD8-18 relative to control females.
The National Research Centre for the Working Environment, Copenhagen, Denmark.
Anne Mette Zenner
AM
Boisen
Thomas
T
Shipley
Petra
P
Jackson
Karin Sørig
KS
Hougaard
Håkan
H
Wallin
Carole L
CL
Yauk
Ulla
U
Vogel
D000818:Animals; D042622:DNA Repeat Expansion / Q000187:drug effects*; D005260:Female; D018095:Germ-Line Mutation / Q000187:drug effects*; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009153:Mutagens / Q000633:toxicity*; D009866:Oogenesis / Q000187:drug effects; D011247:Pregnancy; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D014025:Titanium / Q000633:toxicity*
D009153:Mutagens; C009495:titanium dioxide; D014025:Titanium