Toxicological interactions between nickel and radiation on chromosome damage and repair
- Univ. of Texas Medical Branch, Galveston, TX (United States)
- Kangweon National Univ., Chuncheon (Korea, Republic of)
Carcinogenic nickel compounds are usually found to be weak mutagens; therefore these compounds may not exert their carcinogenic activity through conventional genotoxic mechanisms. On the other hand, the activities of many nickel compounds have not been adequately investigated. We evaluated the genotoxic activities of nickel acetate using conventional chromosome aberration and sister chromatid exchange assays and found that there was no increase of chromosome aberrations or sister chromatid exchanges, although the highest dose (1000 {mu}M) caused mitotic inhibition. In addition, we investigated its effect on DNA repair using our challenge assay. In this assay, lymphocytes were exposed to 0.1 to 100 {mu}M nickel acetate for 1 hr during the G0 phase of the cell cycle. The cells were washed free of the chemical and, 1.5 hr later, were irradiated with two doses of {gamma}-rays (75 cGy per dose separated by 60 min). A significant dose-dependent increase of chromosome translocations was observed (p<0.05). The increase is more than expected based on additive effects from exposure to nickel or {gamma}-rays individually. In contrast to the increase of chromosome translocations, there was no increase in chromosome deletions, although there was a nickel dose-dependent reduction of mitotic indices. Our data suggest that pretreatment with nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair. Furthermore, we suggest that nickel-induced abnormal DNA repair may be a mechanism for its carcinogenic properties. The DNA repair problems that we observed after exposure to low doses of nickel may be viewed as a type of adaptive response. Contrary to some investigators who showed that adaptive responses may be beneficial, our data indicated that some responses may cause more problems than expected. 39 refs., 3 figs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 494141
- Report Number(s):
- CONF-9207255-; ISSN 0091-6765; CNN: Grant NIH R01 ES 04926-02; Contract IAC 1461; TRN: 97:002100-0003
- Journal Information:
- Environmental Health Perspectives, Vol. 102, Issue Suppl.9; Conference: 4. European ISSX meeting: toxicological evaluation of chemical interactions: relevance of social, environmental and occupational factors, Bologna (Italy), 3-6 Jul 1992; Other Information: PBD: Nov 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents
Assays of three carcinogen/non-carcinogen chemical pairs for in vivo induction of chromosome aberrations, sister chromatid exchanges and micronuclei