Increased mutagen sensitivity in human cultured fibroblasts with constitutively high micronucleus levels.
The induction of micronuclei (MN) by incubation with different mutagenic agents was tested in diploid fibroblast cultures obtained from 15 probands with constitutively high MN rates (15.75-77.25 MN/500 cells; average 36.27 +/- 17.60 MN) and 15 probands (controls) with low MN rates (4-13.75 MN/500 cells; average 8.97 +/- 2.73 MN). In order to find out whether fibroblast cultures of individuals with increased spontaneous MN levels exhibit an increased sensitivity to various agents with different genotoxic mechanisms, we studied the induction of MN in these cell cultures by ultraviolet (UV) irradiation, mitomycin C (MMC), N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and benzo-(a)pyrene-diol-expoxid (BPDE). In addition, we tested aphidicolin (APC), a polymerase alpha inhibitor, which is a potent inducer of common fragile sites. Probands with spontaneously high MN showed an significantly increased sensitivity to UV (p less than or equal to 0.005), MMC (p less than or equal to 0.005), and BPDE (p less than or equal to 0.005). No significant differences were found for MNNG and APC as compared to controls.
Rümmelein
B
B
Unit of Toxicogenetics, University of Hamburg, Germany.
Drieschner
O
O
Ehlert
U
U
Weichenthal
M
M
Breitbart
E W
EW
Rüdiger
H W
HW
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology; D016590:Aphidicolin / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology*; D012016:Reference Values; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D014466:Ultraviolet Rays
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D016590:Aphidicolin; D016685:Mitomycin; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide