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Chromosomal changes in cell lines from mouse tumors induced by nickel sulfide and methylcholanthrene
N T Christie1, D M Tummolo, N W Biggart
1Institute of Environmental Medicine, New York University Medical Center, New York 10987.
Abstract:
Rhabdomyosarcomas were induced in mice by intramuscular injections of crystalline nickel sulfide and 3-methylcholanthrene. At early passage, karyotypes were performed by G-banding for four nickel sulfide cell lines and for three 3-methylcholanthrene cell lines. Six cell lines were near-diploid and one nickel sulfide line was near-tetraploid. Three of the nickel sulfide cell lines were characterized by a rearranged marker chromosome which was present in a majority of the cells of each line. The rearrangements leading to the formation of marker chromosomes were different in each nickel sulfide cell line but involved chromosome 4 in two of the nickel sulfide cell lines. Extra copies of chromosome 15 were present in two nickel sulfide cell lines. Possible rearrangement and/or gene activation was examined for the c-mos oncogene on chromosome 4 and the c-myc oncogene on chromosome 15, but no alteration or activation was observed. None of the 3-methylcholanthrene cell lines contained rearranged marker chromosomes; however, one MCA cell line did contain large numbers of double minutes. In all cell lines, minichromosomes (small atypical acrocentric chromosomes) were observed that contained distinct centromeric regions but no other G-positive bands.
Insights
Nickel sulfide and 3-methylcholanthrene induced rhabdomyosarcomas in mice, revealing distinct chromosomal abnormalities. Nickel sulfide cell lines showed rearranged marker chromosomes, while 3-methylcholanthrene lines had double minutes.
Area of Science:
- Oncology
- Genetics
- Toxicology
Background:
- Rhabdomyosarcomas are malignant tumors affecting muscle tissue.
- Chemical carcinogens like nickel sulfide and 3-methylcholanthrene are used to induce these tumors in animal models for research.
- Understanding the chromosomal changes associated with induced rhabdomyosarcomas is crucial for carcinogenicity studies.
Purpose of the Study:
- To investigate the early chromosomal alterations in rhabdomyosarcomas induced by nickel sulfide and 3-methylcholanthrene in mice.
- To characterize the karyotypes of these induced cell lines and identify specific genetic rearrangements.
Main Methods:
- Induction of rhabdomyosarcomas in mice via intramuscular injections of crystalline nickel sulfide and 3-methylcholanthrene.
- Karyotyping using G-banding on early passage cell lines derived from induced tumors.
- Analysis of specific oncogenes (c-mos and c-myc) for potential alterations.
Main Results:
- Six of the seven cell lines were near-diploid, with one nickel sulfide line being near-tetraploid.
- Three nickel sulfide cell lines exhibited unique rearranged marker chromosomes, with chromosome 4 involved in two instances.
- Extra copies of chromosome 15 were noted in two nickel sulfide lines; no c-mos or c-myc alterations were found.
- 3-methylcholanthrene cell lines lacked rearranged markers but one showed numerous double minutes.
- All cell lines contained minichromosomes with distinct centromeric regions.
Conclusions:
- Nickel sulfide and 3-methylcholanthrene induce distinct chromosomal aberrations in mouse rhabdomyosarcomas.
- Rearranged marker chromosomes and extra chromosome copies are characteristic of nickel sulfide-induced tumors.
- Double minutes in 3-methylcholanthrene-induced tumors suggest a different mechanism of oncogenesis or chromosomal instability.
