Is Alkylating Agent “Priming” a DNA Repair Phenomenon?
In the late sixties Jeney, Connors and Jones (1) showed that a low dose of merophan could reduce the toxicity of a second high dose of the same drug or melphalan. Similar protection against radiation-induced death was also demonstrated when mice were pretreated with colchicine or vinca alkaloids (2). In 1975 Millar and coworkers showed that the recovery of bone marrow CFUs, in mice receiving a small dose of cyclophosphamide 2 days before a high dose of busulphan, was enhanced (3). The same group has since shown that the enhanced recovery of normal tissue is not accompanied by a protective effect towards the tumour (4,5). This phenomenon has been called “priming” and has been demonstrated using a range of drugs including cytosine arabinoside (AraC) as the “priming” (i.e. small dose) agent. Notable exceptions are radiation and busulphan (6).
KeywordsVinca Alkaloid Challenge Dose Chinese Hamster Cell Late Sixty Human Bone Marrow Cell
Unable to display preview. Download preview PDF.
- 1.Jeney A jr, Connors TA, Jones M: The toxicity of merophan after treatment with subtoxic dose. Acta Physiol Acad Scien Hung Tomus (33): 89–94, 1968.Google Scholar
- 2.Smith WW, Wilson SM: Effects of vinblastine and vincristine on survival and haemopoiesis in irradiated mice. J Nat Can Inst (39): 1055–1066, 1967.Google Scholar
- 4.Millar JL, McElwain TJ: Combinations of cytotoxic agents that have much less than expected toxicity on normal tissues in mice. Antibiotics Chemother (23): 271–282, 1978.Google Scholar
- 6.Millar JL, Blackett NM, Hudspith BN: Enhanced post-irradiation recovery of the haemopoietic system in animals pretreated with a variety of cytotoxic agents. Cell Tissue Kinet (II): 543–553, 1973.Google Scholar
- 9.Evans BD, Smith IE, Clutterbuck RD, Millar JL: Prevention of acute deaths in mice after very high dose cyclophosphamide by a divided dose schedule. Br J Cancer (48):(In press).Google Scholar