Radiation response of xenografts of a human squamous cell carcinoma and a glioblastoma multiforme: a progress report.
Human cell lines derived from squamous cell carcinomas of the pharynx (FaDu and HSCC6) and glioblastoma multiforme (U87, A2, A7, MMC-1, MMC-2) have been studied in vitro as monolayers in exponential (all 7 cell lines) or plateau phase (FaDu and U87), and as 1 mm diameter spheroids in vitro (FaDu and U87) and as 6 mm diameter xenografts growing in the legs of athymic NCr(nu/nu) nude mice (FaDu, HSCC6, U87, A7 cells). For SF2s and D values, there was broad overlap of values between SCC and glioma cell lines. In contrast, the D0 values were higher for U87, A2, A7, and MCC-1 than the two SCC cell lines, while the extrapolation numbers were greater for the two SCC lines than any of the glial tumor lines (these differences were not regularly significant). Complete dose response assays for local control of FaDu, HSCC6, U87, and A7 xenografts have been performed under conditions of normal blood flow and clamp hypoxia for tumors growing in mice which had received 6 Gy WBI at 24 hr before transplantation. Under the latter circumstances, irradiations have been performed on FaDu and U87 as single doses or as 2, 4, or 8 equal doses; for the fractionated irradiation, treatments were given on a BID basis with 4 hr between the treatments on any 1 day. For irradiation of 1 mm diameter spheroids, radiation was administered as single doses under conditions of equilibration with AIR. The TCD50 for the FaDu was significantly higher and the dose response curve steeper for tumors growing in immune suppressed (6 Gy WBI 24 hr prior to transplantation) than in control nude mice. Tumors, exponential or plateau phase cells, and spheroids derived from U87 were significantly and substantially more resistant under all conditions and fractionation schedules than for FaDu. Thus, the in vitro results do not indicate a clearly greater resistance by the glioma cell lines, while the more limited TCD50 data (single dose and 8 fractions irradiation) show more resistance in vivo by the glial tumors. We noted that the TCD50 values for U87 and A7 glial tumors overlap those for spontaneous tumors of the C3H mouse but are higher than the human squamous cell carcinoma xenografts in the nude mice. Substantial additional data from xenografts are needed to determine if the higher TCD50 values for GBMs, especially for fractionated irradiation, is a regular finding and is of sufficient magnitude to be pursued by studies to explain the observed differences.
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Edwin L. Steele Laboratory of Radiation Biology, Department of Radiation Medicine, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Zietman
A
A
Tomkinson
K
K
Ramsay
J
J
Gerweck
L
L
Sedlacek
R
R
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D002449:Cell Aggregation; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D010610:Pharyngeal Neoplasms / Q000532:radiotherapy; D011836:Radiation Tolerance; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000528:radiation effects