Nonrandom chromosomal alterations in nickel-transformed Chinese hamster embryo cells

The purpose of this study was to determine whether nickel-transformed Chinese hamster cells exhibit nonrandom chromosomal alterations involving heterochromatic regions, particularly the heterochromatic long arm (q) of the X-chromosome, since nickel was previously shown to induce acute chromosomal damage predominantly in heterochromatin. Early passage male or female Chinese hamster embryo cells were transformed to anchorage independence in soft agar following treatment with 10 micrograms/ml NiS, 1 mM NiCl2, or with 10 micrograms/ml 3-methylcholanthrene (MCA). Nickel treatment of Chinese hamster embryo cells resulted in a 2- to 3-fold higher frequency of male (7 of 13) as compared with female (2 of 12) anchorage independent cultures, whereas MCA treatment resulted in equal proportions of male and female anchorage independent cultures. A single soft agar (SA) clone from each of the nickel- or MCA-transformed cultures was karyotyped. Most of the transformed clones had modal chromosome numbers in the diploid range. Four of the 7 male nickel-transformed SA clones exhibited complete or partial deletions of Xq, while one male and one female nickel-transformed SA clone both had an X;5 translocation. In contrast, all of the MCA-transformed SA clones possessed at least one intact X-chromosome. Anchorage-dependent nickel-treated cultures all displayed normal X-chromosomes, suggesting that the Xq deletion was not merely associated with nickel treatment. Structural chromosome alterations were evident in all but one of the anchorage-independent SA clones. None of the anchorage-dependent nickel-treated cultures had rearrangements, although they were generally trisomic for a combination of chromosomes 3 or 3q, 5, and 8. Trisomy of chromosome 3 or 3q occurred in those clones which were tumorigenic in nude mice. Trisomy of chromosome 4 or 4p was a common change which occurred in four nickel-transformed SA clones and a single MCA-transformed SA clone.