Micronucleus formation in cultured human keratinocytes: Involvement of intercellular bioactivation.
Micronucleus formation in cultured human keratinocytes was studied after exposure to benzo[a]pyrene, cyclophosphamide and 12-O-tetradecanoylphorbol-13-acetate without the addition of an exogenous metabolizing system. The first two agents need bioactivation by specific isoenzymes of cytochrome P-450 to form genotoxic intermediates. Benzo[a]pyrene induced the micronucleus formation in both uninduced and Aroclor 1254-pretreated cultures. Clastogenic effects of cyclophosphamide were observed only in Aroclor 1254-pretreated cells. The tumour promotor 12-O-tetradecanoylphorbol-13-acetate did not affect the frequency of micronuclei in human keratinocytes. The data indicate that cultured human keratinocytes can be used to study the tissue-specific response to genotoxic agents as well as interindividual variation in biotransformation capacity.
van Pelt
F N
FN
RCC NOTOX BV, Hambakenwetering 7, 5231 DD's-Hertogenbosch, The Netherlands; Research Institute of Toxicology, University of Utrecht, PO Box 80176, 3508 TD Utrecht, The Netherlands.
Haring
R M
RM
Weterings
P J
PJ