Radiosensitivity of small‐cell lung cancer xenografts compared with activity of c‐myc, N‐myc, L‐myc, c‐raf‐1 and K‐ras proto‐oncogenes

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Abstract
Oncogenes of the myc family c-raf-I and K-ras have been reported to modulate radiosensitivity. We examined the possible relationship between in vivo radiosensitivity to single-dose irradiation with 3-10 Gy, and activity of these proto-oncogenes in 2 sets of small-cell lung cancer (SCLC) xenografts, the CPH and the GLC series. CPH-54A and CPH-54B are in vitro-derived subclones of a SCLC cell line, while the GLC tumours were established as cell lines from a patient during longitudinal follow-up. Both tumours were later transferred into nude mice. CPH-54A was more sensitive to single-dose irradiation than CPH-54B, while, with respect to the 3 GLC tumours examined, GLC-16 was most sensitive, followed by GLC-14 and GLC-19. The CPH tumours expressed similar amounts of c-myc and c-raf-I mRNA, and neither expressed N-myc or L-myc. GLC-14 expressed N-myc and c-raf-I mRNA but no c-myc. GLC-16 and GLC-19 expressed identical amounts of c-raf-I and high levels of c-myc mRNA, but neither expressed N-myc or L-myc. None of the tumours was mutated at codon 12 of K-ras. Our results show that SCLC xenografts with different radiosensitivity may express identical amounts of some of the proto-oncogenes reported to modulate radiosensitivity. Thus, factors other than activation of the examined proto-oncogenes must be involved in causing the differences in radiosensitivity found in the SCLC xenografts. Possible long-term effects of irradiation on proto-oncogene expression was examined in xenografts of GLC-16, following regrowth after single-dose irradiation. No long-term difference in expression of c-raf-I or c-myc mRNA was detected between control tumours and tumours irradiated with 5 or 10 Gy.