Valuation of organism individual sensitivity to carcinogenes action

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Mendeleyev Russian Research Institute for Metrology

VALUATION OF ORGANISM INDIVIDUAL SENSITIVITY TO CARCINOGENES ACTION

V.S.Sibirtsev

M.L.Tyndyk

Benzo[a]pyrene (BP) is one of the most widespread and dangerous among carcinogenes. It will be formed, in particular, as a result of partial combustion of various organic substances. However, the individual sensitivity of the people to BP (as well as to other carcinogenes) is rather various [1-3].

For revealing of this phenomenon mechanism we was taken group of rats, which BP was entered in the form of a water-lipid emulsion unitary (in dozes 100 or 200 mg/kg) or repeatedly (on 10 mg/kg - 10 time with a interval of 10 days). As far as ВР able to render on organism not only carcinogenic, but also all-toxicy action, as parameter, describing individual sensitivity of rats to presence BP, we chose the common life duration of the animals after beginnings of BP inject to him. This parameter was compared to a total output of (+)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-BP - main carcinogen BP metabolite) in animals urine, what was canvassed during the first 5 days after each BP inject to him and analyzed on specially techniques developed by us [4-7]. Thus, the term - 5 days was chosen, as far as (as was established during preliminary researches) for this time is removed the main quantity of BP, after the it inject in rats.

The results of conducted researches are shown on fig.1-4. Of these data it is possible to make following conclusions.

1. For BP (outside of dependence on a mode of its inject in organism) takes place about equal contribution of carcinogenic and all-toxicy effects in reduction of rat life duration.

2. The mode of multiple BP inject in organism is more sparing in comparison with a mode of single BP inject in the same total doze because in the latter case a direct excretion of the BP active forms from organism will be realized only, whereas in the first of considered cases organism "includes" addition mechanismes of adaptation (such, for example, as BP enzyme deactivation).

3. Duration of rats life after beginnings of the BP inject correlates (with a sufficient degree of reliability) with a content (+)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in animal urine.

This conclusions, as we consider, can be are extrapolation on the peoples too (take account of course the distinctions in speed metabolizm of the people and rat and etc). It, in particular, can serve the basis for development of a technique, enabling to reveal the persons, the most subject to negative effect of carcinogenes, that to have a opportunity to apply under the attitude to them appropriate measures.

Fig.1. Change of average on group parameters depending on a doze and mode benzo[a]pyrene (BP) inject.

On abscissa axis are shown: А - number of injects, В,D,E - total doze of BP inject;

on ordinate axis are shown: А,B - average on group total content of (+)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-BP) in animals urine at the first 5 days after BP inject to him; D - average on group duration of rat life; E - percent of animals in group, at which after BP inject internal bodies tumpures were formed (1), underskin tumpures were formed (2) or tumpures were not formed (3).

The symbol “#” marks a mode of multiple BP inject in organism (on 10 mg/kg with a interval of 10 days); symbol “*“ - marks a significances of parameter, authentically (p < 0.05) distinguished from next with them of significances.

Fig.2. Dependence of individual rat life duration (?) from total content 7,8-BP in animals urine (С) at the first 5 days after single BP inject to him in a doze 100 (А) and 200 (B) mg/kg.

Conditional designations on figure: the points 1-3 designate experimental data for the animals, at which after the BP inject: 1 - internal bodies tumpures were formed, 2 - underskin tumpures were formed, 3 - tumpures were not formed; the points 4 and 5 designate data, which were eliminated pursuant to a technique, described in paper [7], for 2 and 3 animals groups, accordingly.

The lines designate regression equations were calculated for: I - all researched animals group

(fig.А - ? = 12,2хC, correlation factor r=0,510, reliability p<0,05; fig.B - ? = 3,15хC, r=0,484, p<0,05);

II - animals, at which after the BP inject internal bodies tumpures were formed

(fig.А - ? = 178 + 3,23хeC/10, r=0,917, p<0,01; fig.B - ? = 167 + 0,014хeC/10, r=0,893, p<0,01).

Fig.3. Dependence of individual rat life duration (?) from total content 7,8-BP in animals urine (С) at the first 5 days after 3 inject at the multipe BP inject to him (in a doze 10 mg/kg - 10 time with a interval of 10 days).

Conditional designations on the schedule for points - same, as on fig.2.

The lines designate regression equations were calculated for:

I - all researched animals group (? = 477 - 15,6хC - 309хe-C, r=0,372, p<0,05); body benzopyrene carcinogen aromatic

II - animals, at which after the BP inject internal bodies tumpures were formed

(? = 454 - 17,5хС - 296хe-C, r=0,547, p<0,05).

Fig.4. Dependence of individual rat life duration (?) from relation of total contents 7,8-BP in him urine at the first 5 days after 3 and 1-й injects (К) at the multiple BP inject to animal organism (in a doze 10 mg/kg - 10 time with a interval of 10 days).

Conditional designations on the schedule for points - same, as on fig.2.

The lines designate regression equations were calculated for:

I - all researched animals group (? = 265 - 377хК + 147хеК, r=0,392, p<0,05);

II - animals, at which after the BP inject internal bodies tumpures were formed

(? = 121хеК, r=0,663, p<0,01) .

References

1. IARC Monographs on the Evaluation of Carcinogenic Risk to Humans. Supp. 7, IARC (Lyon, France), 1987.

2. A. J. LIKHACHEV, D. SH. BENIASHVILI, V. J. BYKOV еt. all: Environ. Health Perspecti. 98, 211.

3. A. J. LIKHACHEV, M. A. ZABEZHINSKIJ, V. J. BYKOV еt. all: Cancer Letters. 78, 163.

4. I. V. SAVOCHKINA, P. P. DIKUN, M. A. ZABEZHINSKIJ еt. all: Questions of Oncology, 36, 1221 (in Russian).

5. A. J. LIKHACHEV, M. A. ZABEZHINSKIJ, P. P. DIKUN еt. all: Questions of Oncology, 38, 950 (in Russian).

6. M. A. ZABEZHINSKIJ, A. J. LIKHACHEV, V. J. BYKOV еt. all: Experimental Oncology, 16, 431 (in Russian).

7. V. S. SIBIRTSEV, M. L. TYNDYK, S. D. IVANOV: Questions of Oncology, 46, 594 (in Russian).

Abstracts

Dynamics of excretion from organism and deactivation of the benzo[a]pyrene (BP - one of the most widespread and dangerous among carcinogenes) is investigated on a example of rats. Is shown, that duration of rats life after beginnings of the BP inject correlates with a content (+)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene in animal urine (were determined on specially techniques developed by us). Besides is shown, that the individual sensitivity to carcinogen in case of single BP inject is mainly determined by efficiency of excretion of the BP active forms from organisms, whereas after multiple BP inject in organism it is determined by mechanisms of BP enzyme deactivation.

Key words: carcinogenes, benzo[a]pyrene.

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