The effect of simultaneous exposure to bromodeoxyuridine and methyl methanesulphonate on sister-chromatid exchange frequency in cultured human lymphocytes.
Assessment of genotoxicity in cultured cells or in experimental animals through the measurement of sister-chromatid exchanges (SCEs) commonly requires their simultaneous exposure to both the test agent and bromodeoxyuridine (BrdUrd). This dual exposure could lead to modified responses because of either synergistic or antagonistic interactions. Differences in protocol may also have their effect. There is, for example, time for DNA repair to take place in protocols in which there is separate exposure to the test agent and BrdUrd, such as human genetic monitoring studies. In this study, human lymphocyte cultures have been used to investigate the effect of the duration of simultaneous exposure to the mutagen methyl methanesulphonate (MMS) and to BrdUrd on SCE incidence. There was a direct relationship between SCE frequency and the time of simultaneous exposure to MMS and BrdUrd that was not dependent on either the total culture time or the total time of exposure to BrdUrd. This suggestion of an interaction between MMS and BrdUrd in inducing SCEs has important implications for the interpretation of SCE data in both experimental and human monitoring studies.
Edwards
A J
AJ
BIBRA Toxicology International, Carshalton, Surrey, UK.
Moon
E Y
EY
Anderson
D
D
McGregor
D B
DB
D000704:Analysis of Variance; D001973:Bromodeoxyuridine / Q000633:toxicity*; D002478:Cells, Cultured; D004347:Drug Interactions; D005188:False Negative Reactions; D005189:False Positive Reactions; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D015203:Reproducibility of Results; D012854:Sister Chromatid Exchange; D013997:Time Factors
D009153:Mutagens; D008741:Methyl Methanesulfonate; D001973:Bromodeoxyuridine