Evaluation of TNF-alpha effects on radiation efficacy in a human lung adenocarcinoma model.
This study sought to determine if pretreatment with low-dose tumor necrosis factor-alpha (TNF-alpha) can enhance the effects of radiation in an NCI-H441 human lung tumor xenograft model. In vitro assays were performed on spleen cells, blood leukocytes, and plasma from the animals, as well as on cultured tumor cells. Tumors in animals given only TNF-alpha grew as well as, or better than, tumors in their untreated counterparts at all time-dose regimens employed. In contrast, early treatment with a total radiation dose of 16 Gy resulted in complete tumor inhibition, whereas 8 Gy modestly (but significantly, P < 0.05) slowed tumor progression. However, the administration of TNF-alpha (4 x 10(4) total units/mouse) 16-18 h prior to irradiation (8 Gy total dose) enhanced the antitumor effects of radiation when treatment was initiated early (P < 0.05). Oxygen radical production and response to mitogenic stimulation by splenocytes were greatest in untreated tumor-bearing animals. Total leukocyte counts in mice given radiation or TNF-alpha + radiation were low, and treatment-related changes were found in percentages of neutrophils and lymphocytes. In vitro assays of tumor cells showed that TNF-alpha + radiation resulted in greater suppression of clonogenic survival and incorporation of [3H]TdR and [3H]UdR incorporation than either agent alone. These results suggest that the use of low-dose TNF-alpha together with radiation may be beneficial in the clinical setting and so warrant further investigation.
Gridley
D S
DS
Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, CA, USA.
Andres
M L
ML
Garner
C
C
Mao
X W
XW
Slater
J M
JM
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004273:DNA, Neoplasm; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha