Different genotoxic profiles between depleted and enriched uranium.

Uranium is an alpha-particle-emitting heavy metal. Its genotoxicity results from both its chemical and its radiological properties that vary with its isotopic composition (12% enriched uranium in (235)U (EU) has a specific activity 20 times higher than 0.3% depleted uranium in (235)U (DU)). The influence of the isotopic composition of uranium on its genotoxic profile (clastogenic/aneugenic) has never been described. The present study evaluated genotoxic profile of uranium with the cytokinesis-block micronucleus centromere assay. C3H10T1/2 mouse embryo fibroblasts were contaminated with either DU or EU at different concentrations (5 microM, 50 microM and 500 microM). Cells received low doses ranging from 0.3 microGy to 760.5 microGy. The frequency of binucleated cells with one micronucleus increased with increasing concentrations of both DU and EU in the same way. EU induced more centromere-negative micronuclei and nucleoplasmic bridges than DU. A correlation between these two clastogenic markers and ionizing radiation doses was observed. Finally, this study showed that the genotoxic profile of uranium depends on its isotopic composition. DU and EU are low and high clastogens, respectively. However, DU aneugenic effects remain high. Thus, there is a need to study the potential role of aneugenic effects of DU in carcinogenic risk assessment linked to uranium internal exposure.

Otoacoustic detection of risk of early hearing loss in ears with normal audiograms: a 3-year follow-up study.

INTRODUCTION: Distortion product otoacoustic emissions (DPOAEs) are known to represent the contractile amplifier function of cochlear outer hair cells. It is known that low or absent DPOAEs are associated with hearing loss on audiograms. However, low DPOAEs can also be found associated with normal audiograms. It is unknown whether low DPOAEs in normal hearing ears are risk markers for subsequent early hearing loss when subjects are exposed to noise. MATERIALS AND METHODS: A 3-year follow-up study was carried out on a population of pilots aged 20-40 years (n=521). Data collection consisted of tonal audiograms, DPOAEs measurements with a calculation of an index of abnormality (the IaDPOAE). Of the 521 pilots enrolled, 350 (67%) had follow-up data 3 years later. In pilots with normal audiograms (n=219, all frequencies=10dB HL), we observed the occurrence of hearing threshold shifts after 3 years depending on whether the IaDPOAE was initially high (group 1) or low (group 2). We used this index to test the hypothesis that reduced DPOAEs levels are potential ear vulnerability biomarkers in apparent normal hearing ears. After a 3-year follow-up, the initial IaDPOAE in normal hearing subjects was correlated with final noise-induced hearing threshold shifts at high frequencies (p<0.01). The occurrence of abnormal audiograms was significantly higher in group 1 compared to group 2 (p=0.003). In group 1, 13% of audiograms were found with at least one frequency 25dB HL compared to 3% of audiograms in group 2. In both groups, impairments occurred at high frequencies and hearing in the 4kHz frequency range was significantly more impaired in group 1 (p=0.035). Group 1 was associated with a relative risk of 2.29 (95% CI 1.26-4.16, p=0.005) of sustaining early hearing loss. There was no significant differences between groups for age and noise exposure. DISCUSSION: In adults with a normal audiogram, ear vulnerability to noise could be elicited by the use of objective DPOAE measurements. A high IaDPOAE that corresponded to reduced DPOAE levels constitutes a risk for early hearing loss. This study emphasised the interest of DPOAE measurements in public health and occupational noise prevention policies. The IaDPOAE calculation may also be interesting for clinicians because no DPOAE index of abnormality is currently available.