1’ !. 4. 671-679, September /995 Cancer Epidemiology. Biomarkers & Prevention 671 Influence of Sex on Cytogenetic End Points: Evidence from a Large Human Sample and Review of the Literatur& Stefano Bonassi,2 Claudia Bolognesi, Angelo Abbondandolo, Roberto Barale, Paola Bigatti, Lamberto Camurri, Leda Dalpra’, Marcella De Ferrari, Alessandra Forni, Cecilia Lando, Paola Padovani, Rosanna Pasquini, Mario Stella, and Riccardo Puntoni Servi,io di Epideistiologia Atobientale. Istituto Nationale per Ia Ricerca wI Cattcro. Largo Rosanna Benti. 10-1-16132 Genoa. Italy IS. B.. C. L.. P. P.. R. P. I. Vnit;I di Valutazione Tossicologica. Centro per lo Studio dci Tuissori di Originc Ati,hientale (CSTA). Istituto Nazionale per Ia Ricerca sul Cancro. Genoa. Italy (C. B.l. Laboratorio di Mutagenesi. Istituto Nazionale per Ia Ricerca sul Cancro, and CSTA. Genoa. Italy A. A.. M. D. Fl: Dipartimento di Scienie dcll’Amhiente e dcl Territorto, University of Pisa. Pisa. Italy IR. B.): Dipartimento di Biologia .Animale-Lahoratori di Antropdogia. University (if Turin. Turin, Italy IP. B.I. Laboratorio di Genetica. Unit#{225} Sanitaria Locale (USE.) 9. Reggio Emilia. Italy IL. C.J: Dipartimento di Biologia e Genetica per Ic Scienze Mediche. University of Milan. Milan. Italy IL. 1)1: Istituto di Medicina dcl Lavoro. Clinica del 1_avoro ‘L. IIk’voto’. University of Mitait. Milan. Italy IA. Fl: Dipartimento di Igiene. University of Perugia. Perugia. halv IR. P.1: and Servizio di Genetica Umana. USL 8. Vicenza NI. 5.1 Abstract The planning and evaluation of human cytogenetic studies should contemplate various confounders and effect modifiers, among these, sex and sex-related factors. The association between this variable and cytogenetic damage has been extensively studied, but conclusive evidence has thus far not been reached, especially for the most recent assays, such as the micronucleus test (MN). In the attempt to quantitatively estimate the sex effect on sister chromatid exchange (SCE), chromosomal aberration (CA), and MN in peripheral blood lymphocytes, we reanalyzed the original data sets of several biomonitoring studies performed over the last decades in 10 Italian laboratories. This approach yielded a very large database, namely 2140, 2495, and 2131 subjects screened for SCE, CA, and MN, respectively. Differences between sexes were expressed in terms of relative risk (RR) of females versus males, after adjustment for age, smoking habits, occupational exposure and inter- and intralaboratory variation. No difference between sexes was found for the frequency of SCE ERR = 1.01; 95% confidence interval (CI) 0.99-1.03] and CA (RR 1.00; 95% CI 0.92-1.08) even if the CI of the RR for SCE includes the 3% excess in females frequently reported by the literature. Conversely, a 29% overall increase of the MN rate in females was observed in the whole data set (RR 1.29; Received 1/4/95: accepted 5/18/95. I This project was supported by Italian Association for Cancer Research, and Applicaiioni Cliniche della Ricerca Oncologica Project of the Italian National Research Council Grants (Contract 92023439 F39). 2 To sshotn requests 11w reprints should be addressed, at Department of Environ- mental Epidemiology. Istituto Nazionale per Ia Ricerca sul Cancro. 1_argo Ros tnna Ben,i. 10 1.16132 Genoa. ltaly. 95% CI = 1.20-1.38). Different trends by age of the MN rate are described in the two sexes, focusing on the peak observed in females in the menopausal period and on the subsequent decrease. Introduction The aim of biomonitoring studies in humans exposed to geno- toxic agents is primarily to identify individuals or populations at increased risk of developing chronic diseases. The most common tests used to assess exposure or early biological effects of genotoxic agents are those showing chromosome damage or sister chromatid exchanges. Typically, these tests are per- formed on peripheral blood lymphocytes in subjects occupa- tionally exposed to agents such as ionizing radiations or chem- ical mutagens. Different confounding factors. such as sex. age. and personal habits. influence the results of these tests and should be considered in the planning and evaluation of human cytogenetic studies. These variables have been estimated to account for up to 20% of the observed interindividual variation in baseline frequency of chromosome damage ( I). The role of sex and sex-related factors in the occurrence of human diseases is well known, and a wealth of evidence is available especially in the field ofcancer. Sex has been reported to be associated with the occurrence of cancer directly. i.e., hormone-related carcinogenesis. or indirectly, acting as a sur- rogate for unknown factors. Numerous investigations aimed to assess the presence of an association between the level of SCE.5 CA, or MN. and sex have thus far been documented, although the size of most of these reports was inappropriate to adequately test this hypoth- esis. An overall evaluation of the population studies on SCE frequency demonstrated the presence of an influence of sex on the interindividual variation of this end point, with a tendency toward a higher number of SCE/cell in women than in men (Table 1). The majority of the reports that considered large scale population studies found a significant difference between sexes, accounting for 2-5% of the total observed variation in baseline SCE rates. The role of the genetic factors on the observed sex differ- enee in SCE frequency have been also investigated in classic 3 The abbreviations used are: SCE. sister chrotnatid exchange; MN. micronticleus test: CA, chromosomal aberration: RR, relative risk: CI, confidence interval: MDL-MI. Istituto di Medicina del Lavoro. Clinica del Lavoro ‘L. [)evoto. University of Milan: DSA-Pl. Dipartimento di Sciente dell’Ambiente e del Temtorio. University of Pisa: ISTI-GE. Laboratorio di Mutagenesi. lsiituto Nazionale per Ia Rieerea sul Canero. Genoa; IGI-PG. Dipartimento di Igiene. University of Perugia: DBA-TO. Dipartimento di Biologia Animale. University of Turin: GEN-RE. Laboratorio di Genetica, USL 9. Reggio Emilia: ONC-GE. Istituto di Oncologia. University of Genoa: USL8-VI. Servizio di Genetica Umana, USL 8. Vicenza; CIT-MI. Laboratorio di Citogenetica. Clinica Ostetrica e Ginecologica. University of Milan: IST2-GE. Unii#{225} di Valutazione Tossico- logica. 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