Melphalan resistant human ovarian tumour cells are cross-resistant to photons, but not to high LET neutrons.
High linear energy transfer (LET) fast neutrons for the local control of advanced head and neck tumours are currently being evaluated at several centres. Fast neutrons are believed to produce more direct, and less OH mediated damage than photons, and consequently be less affected by intracellular thiol levels. Chemoresistant tumours with elevated thiol levels may therefore be more effectively controlled by fast neutron therapy than by photons. The "in vitro" radiation response of melphalan sensitive and resistant human ovarian tumour cell lines has demonstrated that melphalan resistance confers a 1.5-fold level of cross-resistance to photons, primarily attributable to a 2-fold decrease in the alpha component in the resistant OAW42/MER cell line. Pretreatment of the melphalan-resistant line with the thiol depleting agent buthionine sulphoximine (BSO) restored the magnitude of alpha to a value similar to that in the chemosensitive cell line. The survival curves of these cell lines following neutron irradiation were near exponential, with similar values of alpha. This study has demonstrated that melphalan resistant tumour cells are cross-resistant to photon irradiation, but not to fast neutrons. The mechanism of cross-resistance has yet to be determined, but glutathione (GSH) appears to be involved.
Britten
R A
RA
CRC Department Radiation Oncology, University of Liverpool, Clatterbridge Hospital, Bebington, Wirral, U.K.
Warenius
H M
HM
White
R
R
Browning
P G
PG
Green
J A
JA
D005214:Fast Neutrons; D005260:Female; D006801:Humans; D008558:Melphalan / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D011827:Radiation; D011836:Radiation Tolerance / Q000187:drug effects; D014407:Tumor Cells, Cultured
D008558:Melphalan