1992
DOI: 10.1016/0360-3016(92)90514-i
|View full text |Cite
|
Sign up to set email alerts
|

The effect of hypoxia and low pH on the cytotoxicity of chlorambucil

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

2
7
0

Year Published

1993
1993
2011
2011

Publication Types

Select...
6
2
1

Relationship

0
9

Authors

Journals

citations
Cited by 12 publications
(9 citation statements)
references
References 9 publications
2
7
0
Order By: Relevance
“…Cook and Fox (1988) and Chu and Dewey (1988). Wahl et al (1996) Previous studies with non-low pH-adapted cells have shown an enhanced toxicity and/or uptake of chlorambucil at low pHe (Brophy and Sladek, 1983;Mikkelsen et al, 1985;Jahde et al, 1989;Skarsgard et al, 1992;Atema et al, 1993;Parkins et al, 1996) and the opposite effects for mitoxantrone (Jahde et al, 1990;Vukovic and Tannock, 1997). The present experimental results for both normal and acid-adapted cells are consistent with these observations.…”
Section: Resultssupporting
confidence: 88%
“…Cook and Fox (1988) and Chu and Dewey (1988). Wahl et al (1996) Previous studies with non-low pH-adapted cells have shown an enhanced toxicity and/or uptake of chlorambucil at low pHe (Brophy and Sladek, 1983;Mikkelsen et al, 1985;Jahde et al, 1989;Skarsgard et al, 1992;Atema et al, 1993;Parkins et al, 1996) and the opposite effects for mitoxantrone (Jahde et al, 1990;Vukovic and Tannock, 1997). The present experimental results for both normal and acid-adapted cells are consistent with these observations.…”
Section: Resultssupporting
confidence: 88%
“…The in vitro studies also confirmed the predominant role of low pHi in these potentiations by stimulated DNA alkylation of cisplatin and melphalan Atema et al, 1993) and enhanced bioreductive activation of mitomycin C and EO9 (Gibson et al, 1992;Philips et al, 1992;Begleiter and Leith, 1993). Furthermore, we confirmed that chlorambucil is exclusively potentiated at low extracellular pH conditions which, as a weak acid with a pK a value of 5.8, enhances its uptake (Mikkelsen et al, 1985;Skarsgard et al, 1992). The opposite was true for doxorubicin cytotoxicity because of a decreased uptake at low pHe conditions (Alabaster et al, 1989).…”
Section: Discussionsupporting
confidence: 75%
“…This was also in conflict with reports on enhanced cell kill and tumour response to chlorambucil simultaneously given with the vasoactive drugs hydralazine (Skarsgard et al, 1992) or flavone acetic acid (Parkins et al, 1994) to manipulate the pH. Perhaps the effect of drug trapping by a strongly reduced tumour blood flow is more important than a reduced pHe in these responses.…”
Section: Discussionmentioning
confidence: 90%
“…Additionally, the choice of the drugs to evaluate the effect of pH gradient manipulation should exhibit the following characteristics: pK a values in the physiologic pH range, an intracellular site of action and entry to the site of action by passive diffusion through the cell membrane, equivalent cytotoxicity under oxygenated and hypoxic conditions, and stability under relevant pH conditions. The weak acid chlorambucil and weak base doxorubicin meet these criteria (6,12,22,23).…”
Section: Introductionmentioning
confidence: 99%