TY - JOUR
T1 - Mutation induction by charged particles of defined linear energy transfer
AU - Hei, Tom K.
AU - Chen, David J.
AU - Brenner, David J.
AU - Hall, Eric J.
N1 - Funding Information:
The authors take pleasure in thanking Mr Stephen Marino and the RARAF staff for performing the dosimetry and irradiation. Thanks are due to Mr Steven Kushner and Ms Miriam Weisbrot for their expert technical assistance, and to Ms Miriam Battle for preparing the manuscript. This work was supported in part by Grant CA12536, awarded to the Radiological Research Laboratories by the National Cancer Institute, National Institutes of Health, and by Department of Energy Contract ERW331 awarded to Los Alamos National Laboratory.
PY - 1988/7
Y1 - 1988/7
N2 - The mutagenic potential of charged particles of defined linear energy transfer (LET) was assessed using the hypoxanthineguanine phosphoribosyl transferase locus (HGPRT) in primary human fibroblasts. Exponentially growing cultures of early passaged fibroblasts were grown as monolayers on thin mylar sheets and were irradiated with accelerated protons, deuterons or helium-3 ions.The mutation rates were compared with those generated by 137Cs 7 γ-rays. LET values for charged particles accelerated at the Radiological Research Accelerator Facility, using the track segment mode, ranged from 10 to 150 keV/ μtm. After irradiation, cells were trypsinized, subcultured and assayed for both cytotoxicity and 6-thioguanine resistance. For γ-rays, and for the charged particles of lower LET, the dose-response curves for cell survival were characterized by a marked initial shoulder, but approximated to an exponential function of dose for higher LETs. Mutation frequencies, likewise, showed a direct correlation to LET over the dose range examined. Relative biological effectiveness (RBE) for mutagenesis, based on the initial slopes of the doseresponse curves, ranged from 1.30 for 10 keV/ μim protons to 9.40 for 150 keV/ μm helium-3 ions. Results of the present studies indicate that high-LET radiations, apart from being efficient inducers of cell lethality, are even more efficient in mutation induction as compared to low-LET ionizing radiation. These data are consistent with results previously obtained with both rodent and human fibroblast cell lines.
AB - The mutagenic potential of charged particles of defined linear energy transfer (LET) was assessed using the hypoxanthineguanine phosphoribosyl transferase locus (HGPRT) in primary human fibroblasts. Exponentially growing cultures of early passaged fibroblasts were grown as monolayers on thin mylar sheets and were irradiated with accelerated protons, deuterons or helium-3 ions.The mutation rates were compared with those generated by 137Cs 7 γ-rays. LET values for charged particles accelerated at the Radiological Research Accelerator Facility, using the track segment mode, ranged from 10 to 150 keV/ μtm. After irradiation, cells were trypsinized, subcultured and assayed for both cytotoxicity and 6-thioguanine resistance. For γ-rays, and for the charged particles of lower LET, the dose-response curves for cell survival were characterized by a marked initial shoulder, but approximated to an exponential function of dose for higher LETs. Mutation frequencies, likewise, showed a direct correlation to LET over the dose range examined. Relative biological effectiveness (RBE) for mutagenesis, based on the initial slopes of the doseresponse curves, ranged from 1.30 for 10 keV/ μim protons to 9.40 for 150 keV/ μm helium-3 ions. Results of the present studies indicate that high-LET radiations, apart from being efficient inducers of cell lethality, are even more efficient in mutation induction as compared to low-LET ionizing radiation. These data are consistent with results previously obtained with both rodent and human fibroblast cell lines.
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U2 - 10.1093/carcin/9.7.1233
DO - 10.1093/carcin/9.7.1233
M3 - Article
C2 - 3383341
AN - SCOPUS:0023944498
SN - 0143-3334
VL - 9
SP - 1233
EP - 1236
JO - Carcinogenesis
JF - Carcinogenesis
IS - 7
ER -