Hypersensitivity to low single doses and split-dose recovery: two manifestations of induced resistance that might be related.

Purpose: To study retrospectively the relationship between intrinsic radiosensitivity (SF2), and both the low-dose inducible response (alpha(s)/alpha(r)) and the amount of split-dose recovery (betaRR).

Materials And Methods: A total of 53 sets of experimental data obtained with 44 human cell lines were collected from the literature and the above relationships were studied.

Results: Analysis showed a statistically significant correlation between alpha(s)/alpha(r) and SF2 (p = 0.0023, 10 sets of data), and a statistically significant inverse correlation between betaRR and SF2 (p = 0.0005, 36 sets of data, AT excluded). Furthermore, the analysis of the relationship between the challenge dose SF2 (after a clinical-sized priming dose) and that of the single-dose SF2 (27 sets of data, AT excluded) showed a statistically significant correlation (p<0.0001), which deviates from, and becomes higher than, the one-to-one relationship for single-dose SF2<0.30, suggesting that the final response to fractionated irradiation in radiosensitive cells might not be predictable on the basis of simple reconstitution of survival from the single-dose treatment.

Conclusion: The comparison between the two relationships: SF2/(alpha(s)/alpha(r)) and SF2/betaRR, suggests some parallelism indicating that these two phenomena may be inversely correlated and could be attributed to induced resistance mechanisms that might be triggered differently in sensitive and resistant cell lines.