A Simple in-vitro Test for Assessing the Sensitivity of Lymphocytes to Chlorambucil

Lawler, Sylvia D.; Lele, Kusum P.; Pentycross, C. R.

doi:10.1038/bjc.1971.62

Cited by 6 publications

(4 citation statements)

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“…Recently other workers have proposed an in vitro assay system to detect the sensitivity of CLL lymphocytes to chlorambucil (Lawler, Lele and Pentycross, 1971). This procedure is based on the survival of cells cultured continuously in the presence of the drug.…”

Section: Discussionmentioning

confidence: 99%

The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

Hill¹,

Harrap²

1972

Br J Cancer

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It has been shown that lymphocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia do not modify the mustard group of chlorambucil, as has been demonstrated previously in Yoshida ascites cells. However, lymphocytes from patients with an unsatisfactory clinical course or poor response to treatment were able to modify the aromatic region of the drug molecule; little change occurred in the aromatic absorption of intracellular chlorambucil in patients who responded to treatment. This simple test may provide a rapid assessment of a patient's potential response to chemotherapy.

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Section: Discussionmentioning

confidence: 99%

The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

Hill¹,

Harrap²

1972

Br J Cancer

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“…The experiments were set u p with the peripheral blood lymphocytes obtained from 2 controls and 9 patients with CLL. Pure suspensions of lymphocytes were prepared (Lawler et al 1971) and these were washed in TC 199 with heparin (10 u/ml) before setting up the cultures. The culture medium consisted of TC 199 and human AB serum in the proportions of 4:l. The final lymphocyte concentration was approximately 1000/,d.…”

Section: Methodsmentioning

confidence: 99%

“…During the course of the present study, a simple in vitro test, based on cell survival after exposure to drug, was devised to test the sensitivity of lymphocytes to chlor-ambucil (Lawler et al 1971). Lymphocytes from the same controls and patients were used in this study of the effect of the drug on the chromosomes.…”

mentioning

confidence: 99%

Chromosomal Damage Induced by Chlorambucil in Chronic Lymphocytic Leukaemia

Lawler

Lele

1972

Scandinavian Journal of Haematology

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Evidence of chromosomal damage was found in mitogen stimulated cultures of the lymphocytes from patients with chronic lymphocytic leukaemia (CLL), who had been treated with chlorambucil, if sensitivity of the cells to the drug could be demonstrated by an in vitro test (Lawler et al 1971). Additional chromosomal damage was induced when chlorambucil was added to such lymphocytes, in the presence of mitogens, in vitro. On the other hand, if the patients' lymphocytes had previously shown resistance to chlorambucil but little chromosomal damage resulted from therapy or could be induced when the drug was added in in vitro experiments. Chromosomally rearranged lymphocytes found in patients with CLL, who have been treated with chlorambucil, may be interpreted as surviving cells with drug induced changes.

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“…It is stressed, however, that the sharpness of dose-mortality response by ab-The use of 10 normal CLL-lymphocytes to colchicine at concentrations around 10 M (Figure 1) and its reproducibility amongst patients may well conceal other forms of heterogeneity of abnormal cells within and between patients that the use in vitro of X-rays (Schrek et al 1958), chemotherapeutic agents, such as hydrocortisone derivatives (e.g. prednisolone) (Schrek 1964), and chlorambucil (Lawler et al 1971) may reveal.…”

Section: Heterogeneity Of Cll-lymphocytesmentioning

confidence: 99%

Killing and Characterizing Action of Colchicine in vitro on Lymphocytes of Chronic Lymphocytic Leukaemia

Thomson

O'Connor

Wetherley‐Mein

1972

Scandinavian Journal of Haematology

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Circulating lymphocytes in chronic lymphocytic leukaemia (CLL) that die in vitro in 1 day of culture with 10‐7 M‐colchicine (0.04 μg per ml) have been classed as abnormal cells. Most of the increase in peripheral count in 30 patients so far tested (treated or untreated) is due to cells of this type. A colchicine concentration 100, 000 times greater (10‐2 M) kills peripheral populations from healthy individuals in one day. Use of nuclear pyknosis as the index of death has been validated by metabolic and ultrastructural examination of pyknotic lymphocytes. Kinetic studies suggest that initiation of pyknotic degeneration of an abnormal population is achieved at a colchicine concentration of 10‐7 M in ca. 10 hrs — or at higher concentrations in shorter times inversely related to concentration — after attainment of a seemingly critical level of colchicine binding by the population. From comparative cytocidal tests with several structural analogues, and with vinblastine, it is suggested that mode of cytocidal action of colchicine may have a biophysical basis like its antimitotic action involving binding in lymphocytes to micro‐tubular elements. One such analogue, trimethylcolchicinic acid methyl ether (NSC 36354) may be of therapeutic value in treatment of CLL.

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A Simple in-vitro Test for Assessing the Sensitivity of Lymphocytes to Chlorambucil

Cited by 6 publications

References 1 publication

The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

The Uptake and Utilization of Chlorambucil by Lymphocytes from Patients with Chronic Lymphocytic Leukaemia

Chromosomal Damage Induced by Chlorambucil in Chronic Lymphocytic Leukaemia

Killing and Characterizing Action of Colchicine in vitro on Lymphocytes of Chronic Lymphocytic Leukaemia

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