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Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi

Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi

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90 Gülruh Ulako¤lu<br />

According to these results 2, 4 <strong>and</strong> 6 mg/ml<br />

concentrations <strong>of</strong> ADM 24 hours after administration<br />

<strong>of</strong> EAT cells, all concentrations caused a quite<br />

definite cytotoxic effect in comparison to the control,<br />

the most effective concentration was 6 mg/ml. The<br />

cytotoxic effect at 24 hours continued at after 30<br />

hours <strong>and</strong> after 48 hours the cytotoxic effect <strong>of</strong> all the<br />

concentrations increased. According to this<br />

observation, ADM induces a cytotoxic effect on EAT<br />

cells depending on concentration <strong>and</strong> time.<br />

Discussion<br />

EAT cells survive in acidic fluid present in the<br />

peritoneal cavity <strong>of</strong> mice in the form <strong>of</strong> a suspension.<br />

It was known that, after the transplantation into<br />

peritoneal cavity <strong>of</strong> mice the number <strong>of</strong> cells increase<br />

exponentially up to the 9. day <strong>and</strong> reach the<br />

plato-phase following 9. <strong>and</strong> 10. days (Lazebnik et al.,<br />

1991; Song et al., 1993; Vinuela et al., 1991). For this<br />

reason, during the in vivo experiments <strong>of</strong> this study<br />

ADM was injected to mice at the 4. day following<br />

EAT transplantation to them. The reason why ADM<br />

was given in the middle <strong>of</strong> the multiplication period 4.<br />

day to see how it affected the exponential growth <strong>of</strong><br />

EAT cells.<br />

In a study similar to this one, to DBA/2 mice<br />

bearing acidic murine lymphocytic leukemia, ADM<br />

<strong>and</strong> daunorubicin were administered separately <strong>and</strong><br />

their survival periods were controlled. In this study<br />

0.25-2.00 mg/kg ADM was injected to tumor bearing<br />

mice for 5 days. The survival <strong>of</strong> mice, receiving a<br />

high dose prolonged 140 % that <strong>of</strong> the controls <strong>and</strong> 20<br />

% <strong>of</strong> the experimental mice survived up to to 50. day<br />

(Schwartz <strong>and</strong> Grindey, 1973). Even though different<br />

kind <strong>of</strong> tumor bearing mice <strong>and</strong> different<br />

concentrations <strong>of</strong> ADM were used, the results <strong>of</strong> this<br />

experiment also supports theirs.<br />

Experiments on the survival time’s prolongation<br />

started in 1978. Extracts prepared from muscle <strong>and</strong><br />

liver tissues <strong>of</strong> mice were injected i.p. for a period <strong>of</strong><br />

12 days to EAT bearing mice. It was found that these<br />

mice survived longer that the control ones. In<br />

contrast, a positive results were not obtained from<br />

spleen, kidney, lung, serum, skin <strong>and</strong> small intestine<br />

extracts (Tong et al., 1978).<br />

Different doses <strong>of</strong> ADM was investigated in<br />

various cells. It was shown that ADM in 0.2 mg/ml<br />

concentration exerted cytotoxic effect on human<br />

peripheral lymphocytes. In the same study, it was also<br />

observed that this concentration decreased the<br />

multiplication <strong>of</strong> V79 (Chinese hamster’s lung<br />

fibroblast cells) cells 50 % (Szabona, 1996). In our<br />

study, it was also observed that ADM’s 2, 4 <strong>and</strong> 6<br />

mg/ml concentrations exerted a cytotoxic effect on<br />

EAT cells which increased depending on time. When<br />

K562 (human erythroleukemia) cell, propagated in<br />

tissue culture, were treated with 5, 10 <strong>and</strong> 30 mM<br />

ADM, it was determined that the cell number was<br />

decreased in comparison to the control <strong>and</strong> the drug<br />

exerted a cytotoxic effect depending on the dose used<br />

(Ciaccia et al., 1994). It was observed that allogenic<br />

tumor cells <strong>and</strong> mouse spleen cells, propagated in cell<br />

culture, when treated with ADM in an in vitro<br />

medium, ADM exerted a cytotoxic effect on them<br />

(Ehrke et al., 1984; Tomozic et al., 1980). It was also<br />

found that when HeLa cells, propagated in an in vitro<br />

medium, were treated with 5, 10, 25, 50 <strong>and</strong> 100<br />

mg/ml ADM, their survival ratio decreased depending<br />

on the dose (Jagetia <strong>and</strong> Nayak, 1996).<br />

Even though ADM makes cytotoxic effect in<br />

tumor cells, it also exerts negative effects on normal<br />

cells. For this reason, when ADM was administered to<br />

patients in the clinic, drugs which remove its side<br />

effects were also used (Vichi <strong>and</strong> Tritton, 1993).<br />

Many studies are present where ADM is applied in<br />

various doses to many different kinds <strong>of</strong> tumors. In<br />

this study, the results derived from first time this<br />

ADM doses applied to EAT cells are in accordance<br />

with those indicated in literature.<br />

References<br />

Arinaga S, Akiyoshi T <strong>and</strong> Tsuji H. Augmentation <strong>of</strong> the<br />

generation <strong>of</strong> cell-mediated cytotoxicity after a single<br />

dose <strong>of</strong> adriamycin in cancer patients. Cancer Research.<br />

46: 4213-4216, 1986.<br />

Ciaccia M, Tesoriere L, Pintaudi AA, Re R <strong>and</strong> Cardillo SV.<br />

Vitamin A preserve the cytotoxic activity <strong>of</strong> adriamycin<br />

while counteracting its peroxidative effects in human<br />

leukemic cells in vitro. Biochemistry <strong>and</strong> <strong>Molecular</strong><br />

<strong>Biology</strong> International. 34: 329-335, 1994.<br />

Çerçi B <strong>and</strong> Ulako¤lu G. The effects <strong>of</strong> adriamycin on<br />

L-Strain cells. Chimica Acta Turcica. 28: 25-27, 2000.<br />

Ehrke JM, Ryoyama K <strong>and</strong> Cohen AS. <strong>Cell</strong>ular basis for<br />

adriamycin-induced augmentation <strong>of</strong> cell-mediated<br />

cytotoxicity in culture. Cancer Research. 44: 2497-<br />

2504, 1984.<br />

Jagetia CG <strong>and</strong> Nayak V. Micronuclei-induction <strong>and</strong> its<br />

correlation to cell survival in HeLa cells treated with

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