title: Heritability of baseline and induced micronucleus frequencies.
abstract: The scoring of micronuclei (MN) is widely used in biomonitoring and mutagenicity testing as a surrogate marker of chromosomal damage inflicted by clastogenic agents or by aneugens. Individual differences in the response to a mutagenic challenge are known from studies on cancer patients and carriers of mutations in DNA repair genes. However, it has not been studied to which extent genetic factors contribute to the observed variability of individual MN frequencies. Our aim was to quantify this heritable genetic component of both baseline and radiation-induced MN frequencies. We performed a twin study comprising 39 monozygotic (MZ) and 10 dizygotic (DZ) twin pairs. Due to the small number of DZ pairs, we had to recruit controls from which 38 age- and gender-matched random control pairs (CPs) were generated. For heritability estimates, we used biometrical modelling of additive genetic, common environmental, and unique environmental components (ACE model) of variance and direct comparison of variance between the sample groups. While heritability estimates from MZ to DZ comparisons produced inconclusive results, both estimation methods revealed a high degree of heritability (h(2)) for baseline MN frequency (h(2) = 0.68 and h(2) = 0.72) as well as for the induced frequency (h(2) = 0.68 and h(2) = 0.57) when MZ were compared to CP. The result was supported by the different intraclass correlation coefficients of MZ, DZ and CP for baseline (r = 0.63, r = 0.31 and r = 0.0, respectively) as well as for induced MN frequencies (r = 0.79, r = 0.74 and r = 0.0, respectively). This study clearly demonstrates that MN frequencies are determined by genetic factors to a major part. The strong reflection of the genetic background supports the idea that MN frequencies represent an intermediate phenotype between molecular DNA repair mechanisms and the cancer phenotype and affirms the approaches that are made to utilise them as predictors of, for example, cancer risk.
authors.affiliation: Institute of Human Genetics, University Hospital Ulm, Ulm, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Surowy
authors.forename: Antje
authors.initials: A
authors.lastname: Rinckleb
authors.forename: Manuel
authors.initials: M
authors.lastname: Luedeke
authors.forename: Madeleine
authors.initials: M
authors.lastname: Stuber
authors.forename: Anna
authors.initials: A
authors.lastname: Wecker
authors.forename: Dominic
authors.initials: D
authors.lastname: Varga
authors.forename: Christiane
authors.initials: C
authors.lastname: Maier
authors.forename: Josef
authors.initials: J
authors.lastname: Hoegel
authors.forename: Walther
authors.initials: W
authors.lastname: Vogel
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity; D011836:Radiation Tolerance / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: D009153:Mutagens