In vitro chromosome aberration tests using human dental pulp cells to detect the carcinogenic potential of chemical agents.
To examine if human dental pulp cells are useful for assessing the carcinogenic potential of chemical agents, we cultured human dental pulp cells from adults and studied the ability of chemical agents known to be carcinogenic to induce chromosome aberrations in these cells. We confirmed that human dental pulp cells in primary or secondary cultures had the capability of accumulating calcium in vitro as detected by Alizarin red staining and generating dentin-like tissue in immunocompromised mice. These phenotypes were maintained even in cells at seven passages. Next, we examined if chromosome aberrations were induced by exposure of human dental pulp cells (designated here as D824 cells) at seven to nine passages to chemical agents with carcinogenic activity. Statistically significant increases in the frequencies of chromosome aberrations were induced in D824 cells treated with a direct-acting carcinogen, mitomycin C, for 3 h. Chromosome aberrations were also induced at statistically significant levels in D824 cells treated with an indirect-acting carcinogen, cyclophosphamide, for 2 h in the presence of exogenous metabolic activation with rat liver postmitochondrial supernatant. Cyclophosphamide failed to induce chromosome aberrations in the absence of exogenous metabolic activation. Although the reliability of chromosome aberration tests using human dental pulp cells remains to be validated by studying the ability of various other chemical agents with or without carcinogenic activity to induce chromosome aberrations, this chromosome aberration test system may be useful for carcinogenic risk assessment in the target cells.
Tsutsui
Takeo W
TW
Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Inaba
Tomohiro
T
Fisher
Larry W
LW
Robey
Pamela Gehron
PG
Tsutsui
Takeki
T
D000293:Adolescent; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017690:Cell Transplantation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D017077:Culture Media, Conditioned; D003520:Cyclophosphamide / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D003810:Dentinogenesis; D006801:Humans; D008297:Male; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology; D051381:Rats
D017077:Culture Media, Conditioned; D009153:Mutagens; D016685:Mitomycin; D003520:Cyclophosphamide; D002118:Calcium