HGPRT mutation induction by N-ethyl-N-nitrosourea as measured by 6-thioguanine resistance is higher in male than in female Syrian hamster fetuses

BACKGROUND: The consequences of mutations in embryonic and fetal cells are serious and contribute to high prenatal sensitivity to mutagenic agents. An understanding of the factors that influence the yield of such mutations is important for management of adverse effects of perinatal exposures. Resist...

Full description

Saved in:
Bibliographic Details
Published in:Birth defects research. Part B. Developmental and reproductive toxicology 2006-10, Vol.77 (5), p.399-404
Main Authors: Donovan, Paul J., Smith, George T., Dove, Lee F., Klose, John, Powell, Douglas A.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cells, Cultured
Chemical mutagenesis
Cricetinae
Ethylnitrosourea - toxicity
Female
female fetuses
Fetus - drug effects
Fetus - metabolism
HGPRT
Hypoxanthine Phosphoribosyltransferase - genetics
Lyon hypothesis
Male
male fetuses
Medical sciences
Mesocricetus
Mutagenesis - drug effects
N-ethyl-N-nitrosourea
Pregnancy
Sex Characteristics
Thioguanine - pharmacology
Toxicology
X-chromosome inactivation
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:BACKGROUND: The consequences of mutations in embryonic and fetal cells are serious and contribute to high prenatal sensitivity to mutagenic agents. An understanding of the factors that influence the yield of such mutations is important for management of adverse effects of perinatal exposures. Resistance to 6‐thioguanine (6‐TG) can be utilized to study mutational events at the hypoxanthine‐guanine phosphoribosyl transferase (HGPRT) locus. HGPRT is X‐linked and recessive. According to the Lyon hypothesis, male cells have only one X‐chromosome and female cells randomly inactivate the second X‐chromosome. This leads to the prediction that X‐linked genes should be equally sensitive to the mutagenic effects of toxicants in male and female fetuses. METHODS: We tested this supposition by in utero exposure of Syrian hamster fetuses to N‐ethyl‐N‐nitrosourea (ENU) at day 12 of gestation. ENU is a strong carcinogen and mutagen. HGPRT mutations were detected by selection with 6‐TG. RESULTS: Surprisingly. the male cells had 4 to 5 times more 6‐TG mutants than female cells, in two separate experiments (p
ISSN:1542-9733
1542-9741
DOI:10.1002/bdrb.20088