Abstract
Aneuploidy, defined as structural and numerical aberrations of chromosomes, continues to draw attention as an informative effect biomarker for carcinogens and male reproductive toxicants. It has been well documented that aneuploidy is a hallmark of cancer. Aneuploidies in oocytes and spermatozoa contribute to infertility, pregnancy loss and a number of congenital abnormalities, and sperm aneuploidy is associated with testicular cancer. It is striking that several carcinogens induce aneuploidy in somatic cells, and also adversely affect the chromosome compliment of germ cells. In this paper we review 1) the contributions of aneuploidy to cancer, infertility, and developmental abnormalities; 2) techniques for assessing aneuploidy in precancerous and malignant lesions and in sperm; and 3) the utility of aneuploidy as a biomarker for integrated chemical assessments of carcinogenicity, and reproductive and developmental toxicity.
Highlights
Biomarker of effect is defined as a measurable biochemical, physiologic or other alteration in an organism that is associated with an established or possible health impairment or disease [1]
Other historical steps that elucidated the role of aneuploidy in cancer, reproductive, and developmental toxicity include: 1929, Barbara McIntock discovers the disruptive role of aneuploidy in maize development [22]; 1956, Julian Huxley introduces the concept of cancer as a new biological species with a high degree of genetic heterogeneity [23]; 1959, Jerome Lejeun discovers that an extra copy of Chromosome 21 causes Down Syndrome [24]; 1961, Theodore Hauschka documents that the euploid content in human and rodent tissues is strongly conserved and observes that leukemia cells are consistently aneuploid [25]; 1971, Andreĭ Pavlovich Dyban and Vladislav Sergeevitch Baranov show through Robertsonian translocation the reproductive and developmental effects of all the possible trisomies in mice [26]; and 1986, Mitsuo Oshimura and J
Aneuploidy is an excellent candidate as an evidencebased biomarker for reproductive toxicants and carcinogens
Summary
Biomarker of effect is defined as a measurable biochemical, physiologic or other alteration in an organism that is associated with an established or possible health impairment or disease [1]. We will review 1) the role of aneuploidy in cancer and reproductive toxicity; 2) the overlap among chemical classes between sperm genotoxicants, sperm aneuploidogens (substances inducing an altered number of whole chromosomes) and chemical carcinogens; 3) the different techniques available to assess aneuploidy in precancerous and malignant lesions and sperm; and 4) the experimental and epidemiological possibilities for integrating aneuploidy measurement into integrated chemical assessments.
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