The induction of thymidine- and IUdR-resistant variants in P388 mouse lymphoma cells by x-rays, UV and mono- and bi-functional alkylating agents |
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Authors: | D Anderson M Fox |
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Institution: | Paterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester M20 9BX Great Britain |
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Abstract: | Dose-response curves for “mutation” to resistance to 5-iodo-2-deoxyuridine (IUdR) and excess thymidine (TdR) in P388 mouse lymphoma cells have been established after exposure of these cells to six chemical mutagens, UV |and| ionising radiations. The dose-response curves for all mutagens in both selective system show considerable similarities when induced mutation frequencies are plotted against survival. Expression time for both types of variants, IUdRr and TdRr, are similar, i.e. maximum frequencies are reached by 48 h and there is no fall in variant frequency at late expression times up to 144 h. Over the range of survival levels studied there appears to be little or no dependence of expression time on dose of mutagen. Some loss of mutants after high doses (i.e. at low survival levels) was observed due to the fact that a significant proportion of both TdRr and IUdRr clones were more sensitive to the mutagens than the wild-type population. The similarities in induced dose-response curves for different mutagens suggest that the mutants have a common origin, probably an error in repair, but it seems unlikely that errors in “cut and patch” repair are responsible. A comparison of spontaneous frequencies of IUdRr and TdRr variants suggests that IUdR is mutagenic in P388 cells. |
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Keywords: | EMS ethyl methanesulphonate HN2 nitrogen mustard ICR-191 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine dihydrochloride clone resistant to 5-iodo-2-deoxyuridine MDMS methylene dimethanesulphonate MMS methyl methanesulphonate MNNG MNU clone resistant to excess thymidine TEM triethylene melamine |
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