Comparative induction of micronuclei in repair-deficient and -proficient Chinese hamster cell lines following clastogen or aneugen exposures.
The Chinese hamster cell line V79-4 and two ionising radiation-sensitive mutants irs1 and irs3, were used to assess the genotoxic effects of a clastogen (X-rays), an aneugen (podophyllotoxin) and an agent having both activities (etoposide), using the cytokinesis-block micronucleus assay combined with kinetochore labelling. All three agents induced micronuclei in a dose-dependent manner. Between 70 and 90% of the micronuclei induced by X-rays were kinetochore-negative and indicative of clastogenic activity, the relative frequencies of which were increased in the repair-deficient cell lines. In contrast, podophyllotoxin induced mainly kinetochore-positive micronuclei (up to 97%) and could be classified as an inducer of chromosome lagging and was essentially aneugenic in its activity. Micronuclei induced by etoposide were 61-84% kinetochore-negative and 26-39% kinetochore-positive, indicating both clastogenic and aneugenic activity. In the case of both etoposide and podophyllotoxin, there were no observed differences in the induction of micronuclei between the wild-type and repair-deficient cell lines. The data demonstrate the effectiveness of the cytokinesis-block micronucleus/kinetochore assay in determining the mechanisms of action of both chemicals and radiations upon chromosome structure and number and the potential influences of repair upon micronuclei induction.
Hermine
T
T
School of Biological Sciences, University of Wales Swansea, UK.
Jones
N J
NJ
Parry
J M
JM
D000782:Aneuploidy; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002875:Chromosomes / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair; D005047:Etoposide / Q000633:toxicity*; D018386:Kinetochores; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D011034:Podophyllotoxin / Q000633:toxicity*; D011836:Radiation Tolerance; D014965:X-Rays
D009153:Mutagens; D005047:Etoposide; D011034:Podophyllotoxin