Multiple phenotypic divergence of mammary adenocarcinoma cell clones.

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Abstract
We have shown that, with in vitro passage, subclones derived from clonal cell populations of 13762NF mammary adenocarcinoma undergo phenotypic drift and diversification in their cellular properties. Here we examine whether phenotypic divergence of 13762NF cell clones extends to therapeutic treatments used in eliminating mammary tumors and whether the apparent rates of phenotypic divergence vary for different treatments. Six subclones isolated from low passage clone MTF7 (T11 l; tissue culture passage 11) cells were compared to a similar number of subclones isolated from high passage clone MTF7 (T35; tissue culture passage 35) cells. Subclones derived from clone MTF7 (TI l) were relatively homogeneous (not significantly different) in their inherent sensitivities to ionizing radiation, extrapolation coefficients and quasithreshold dose values (Do = 1·61–1·99 Gy; n=0·89–3·42; Dq = 0–2·34). When the MTF7 (Tll) subclones were examined for their sensitivities to 45°C hyperthermic treatment, the inherent sensitivities and dose-response curve parameters (Do = 5·24–10·05 min; n = 1·08–10·47; Dq = 0·78–12·31) were heterogeneous (significantly different). In addition, the MTF7 (T1 l) subclones were heterogeneous (significantly different) in their sensitivities and dose-response curve parameters to 5-fluoro-2′-deoxyuridine (FUdR) treatment (slope= −0·70 to −1·59; y-intercept = 1·31 × 102 to 47·80 × 102). The LD50 values for FUdR ranged from 14–150 nm for the MTF7 (T11) subclones. At high passage MTF7 (T35) subclones were heterogeneous in their dose-response parameters to ionizing radiation (Do = 1·17–2·05 Gy; n = 0·80–41·18; Dq = 1·79-\24·94), hyperthermia (Do = 3·57–6·32 min; n = 2·08–13·54; Dq = 3·68–9·30) and FUdR (slope= −0·77 to −0·93; y-intercept = 4·64 × 102 to 8·83 × 102; LD50 = 50–160nm). The results indicate that clonal cells diverge for distinct phenotypic properties at differing rates to form heterogeneous cell populations with unique sensitivities to various therapeutic treatments.