Charged-particle mutagenesis: I. Cytotoxic and mutagenic effects of high- LET charged iron particles on human skin fibroblasts

Cytotoxic and mutagenic effects of high-LET charged iron (⁵⁶Fe) particles were measured quantitatively using primary cultures of human skin fibroblasts. Argon and lanthanum particles and γ rays were used in comparative studies. The span of LETs selected was from 150 keV/μm (330 MeV/u) to 920 keV/μm (600 MeV/u). Mutations were scored at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus using 6-thioguanine (6-TG) for selection. Exposure to these high-LET charged particles resulted in exponential survival curves. Mutation induction, however, was fitted by the linear model. The relative biological effectiveness (RBE) for cell killing ranged from 3.7 to 1.3, while that for mutation induction ranged from 5.7 to 0.5. Both the RBE for cell killing and the RBE for mutagenesis decreased with increasing LET over the range of 1.50 to 920 keV/μm. The inactivation cross section (σ(i)) and the action cross section for mutation induction (σ(m)) ranged from 32.9 to 92.0 μm² and 1.45 to 5.56 x 10^-3 μm²; the maximum values were obtained by ⁵⁶Fe with an LET of 200 keV/μm. The mutagenicity (σ(m)/σ(i)) ranged from 2.05 to 7.99 x 10^-5 with an inverse relationship to LET.