Sergej P. Osinsky, M.D.,⁽¹⁾, I Levitin⁽²⁾, L Bubnovskaya⁽³⁾, A Sigan⁽⁴⁾, I. Ganusevich⁽⁵⁾, V. Michailenko⁽⁶⁾, T. Kovelskaya^{(7)
(1)(2)(3)(4)(5)(6)(7)}Inst. exp. Pathol. Oncol. Radiobiol. - Kiev . Ukraine

	[Biophysics]	[Oncology]

RESULTS

Acute toxicity of complexes. The acute toxicity was found to be as follows: rat (strain IEPOR bred) - LD_50/14 = 41.6 (AC-11) and 66.7 (AC-30) mg/kg; mice

[F₁ (C57Bl/DBA₂)] - LD_50/14 = 34.2 (AC-11), 68.3 (AC-30) and 69.2 (AC-40) mg/kg.

Antitumor activity of complexes. It was observed that all cobalt complexes of AC-series have produced a substantial anticancer activity. Table 1 shows the response of primary tumor to AC-complexes treatment. It is noticable that the antitumor effect of complexes was not higher than 80%.

 

Table 1. Antitumor activity of "inorganic" cobalt(III) complexes in animals bearing transplanted tumors (inhibition of primary tumor growth, %)

 

Complex	Guerin carcinoma	Walker-256 carcinoma	Mammary adenocarcinoma Ca755	Melanoma B-16
AC-11	72 (n=13)	60 (n=11)	76 (n=15)	50 (n=12)
AC-30	74 (n=10)	62 (n=10)	79 (n=14)	65 (n=17)
AC-40	n.d.	n.d	77 (n=19)	n.d.

Complexes were given at a dose of 15- 20 mg/kg intravenously (rat) or 12 mg/kg intraperitoneally (mice). The treatment was three-four-fold with a two-days break (rat) or ten-fold with a one-day break (mice). The treatment was initiated in 6-7 days (rat) or one-two days (mice) after tumor transplantation.

n - number of animals. n.s. non determined.

 

At the same time it was observed significant antimetastatic effect of complexes in experiments with Lewis lung carcinoma and melanoma B-16 (tables 2-4). It is important that antimetastatic activity of complexes, especially of AC-30, was considerably higher than that of cisDDP or cyclophosphamide (data are not presented).

 

Table 2. Antimetastatic activity of "inorganic" cobalt(III) complexes in mice bearing Lewis lung carcinoma (model without amputation)

 

complex	Number of mice without lung metastases (%)	Inhibition of number of metastases (%) in lung	metastases growth estimated by volume of metastases (%)
AC-11	15 (n=15)	67	70
AC-30	17.5 (n=13)	74	69
AC-40	15 (n=12)	77	78

Complexes were given at a dose of 12 mg/kg intraperitoneally. The treatment was ten-fold with a one day break. n = number of mice.

 

Table 3. Antimetastatic activity of "inorganic" cobalt(III) complexes in mice bearing Lewis lung carcinoma (model with amputation)

 

complex	Number of mice without lung metastases (%)	Inhibition of number of metastases (%) in lung	metastases growth estimated by volume of metastases (%)
AC-11	27.5 (n=20)	67	90
AC-30	34 (n=14)	84	99
AC-40	35 (n=12)	84	95

Complexes were given at a dose of 12 mg/kg. The treatment was ten-fold with a one day break. n = number of mice.

 

Table 4. Antimetastatic activity of "inorganic" cobalt(III) complexes in mice bearing melanoma B-16

 

complex	Number of mice without lung metastases (%)	Inhibition of number of metastases (%) in lung	metastases growth estimated by volume of metastases (%)
AC-11	37.5 (n=12)	75	76
AC-30	40 (n=17)	71	99

Complexes were given at a dose of 12 mg/kg. The treatment was ten-fold with a one-day break. n = number of mice.

 

Modifying activity of complexes. AC-11 or AC-30 given 60 min before LHT (41⁰C, 60 min) produced a tumor growth delay (TGD) of about 10.5 and 15 days, respectively. It must be noted that efficacy of the combined treatment was higher than that of the local heating alone (43⁰C, 60 min) which produced TGD of about 6.5 days.

Table 5 demonstrates the Guerin carcinoma response to radiation alone and supplemented with complex AC-30. One can see the significant potentiation of the radiation effect on Guerin carcinoma by the AC-30: radiation alone at a dose of 20 Gy and radiation at a dose of 10 Gy supplemented with AC-30, given 60 min before radiation, produced in 75% of tumor complete regression, respectively. Hence, the enhancement ratio was found to be 2.0 in this case.

 

Table 5. Radiopotentiating activity of complex AC-30 (15 mg/kg) in rats bearing

Guerin carcinoma (n = number of rats)

Treatment	Tumor growth inhibition (%)	Complete regression of tumor (%)
Control (n=9)	-----	0
10 Gy (n=7)	67	50
AC-30+10 Gy (n=8)	70.5	75
15 Gy (n=6)	90	50
AC-30+15 Gy (n=7)	99	100
20 Gy (n=7)	80	75
AC-30+20 Gy (n=7)	89	75

Discussion Board

Any Comment to this presentation?

[ABSTRACT] [INTRODUCTION] [MATERIALS AND METHODS] [RESULTS] [DISCUSSION] [CONCLUSIONS] [REFERENCES] [Discussion Board]

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	[Biophysics]	[Oncology]

Sergej P. Osinsky, M.D.,, I Levitin, L Bubnovskaya, A Sigan, I. Ganusevich, V. Michailenko, T. Kovelskaya
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Last update: 15/01/00