Genetically susceptible subgroups.
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Biomedical subjects
Publications and source records attributed to L C Strong.
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Three hundred and seventy-one mice of the C3H/St inbreds bearing spontaneous tumors of mammary gland origin have been used in this experiment. All mice studied were lineal descendents of a tumor-bearing mouse which had been injected with a liver extract. In this descent there appears to be a transmissible entity presumably induced by the injection of the liver extract. Following 15 generations of inbreeding after the appearance of a transmissible entity, a second sudden reversal of effect on cancer growth in mice has been indicated. This change has progressively altered the growth of cancer from a very low effect to a maximal effect, i.e., to a complete regression of a high percentage of the tumor. The maximal effect of the transmissible entity is the complete suppression of the growth of cancer during, at least, through the 25th period of observation, thus producing negative values of tumor growth. All these effects of the growth and fate of spontaneous tumors of mammary gland origin in mice have been obtained in a single lineal descent of C3H/St inbreds without resorting to any outcross.
Spontaneous tumour-bearing mice of the C3H/St and subline C3HB/St inbred strains received injections of three nucleosides, adenosine, 6-methyl adenosine, and 5-methyl cytidine, prepared in the same molecular concentration as they had occurred in an alcohol-soluble liver extract which in previous work had suppressed tumour growth. Two transmissible entities appear to be present and they show different degrees of effect upon the growth and regression of spontaneous tumours of mammary gland origin (adenocarcinoma). The first transmissible entity (TE) occurred in the lineal descent of mice following injection of the liver extract. The second entity (TE2) appeared following injection of 5-methyl cytidine. TE manifested its maximum effect in suppressing cancer in mice during the 20th generation of a lineal descent following the injection of the original liver extract into a mother of the cancer proband. TE2 appears to be optimal in controlling cancer in the F11 generation of a second lineal descent derived from an original cancer proband of the C3H/St inbred strain injected with 5-methyl cytidine.
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Tumor-bearing mice of the C3H/ST inbreds were used in this investigation. Of the 598 mice, 290 were controls, 248 received injections of 5-methyl cytidine dissolved in physiological salt solution, and 60 received injections of three nucleosides - adenosine, 6-methyl adenosine, and 5-methyl cytidine - also dissolved in physiological salt solution. The mice were divided into 6 groups based upon the number of generations of descent from a mouse injected with an alcohol-soluble liver extract. The criterion of tumor growth is the average increment of growth at the 20th observation period in the 7th week (3 per week). There is a cumulative inhibition of tumor growth, compared with controls, when 5-methyl cytidine is added to the effect of a transmissible entity which occurs in the lineal descendants of a tumor-bearing mouse injected with an alcohol-soluble liver extract and when the combination of three nucleosides in the same ratio of molar concentrations as in the liver extract is added to the effect of the transmissible entity.
Ten series mice of C3H/ST inbreds with spontaneous tumors have received 5-methyl cytidine (total 500 mice). Graded single doses of (1) 3.86, (2) 2.57, (3) 2.06, (4) 1.54, (5) 1.03, (6) 1.54, (7) 1.03, (8) 0.51, (9) 0.26, and (10) 0.13 mg/injection (three times weekly) were used. In series 1-5 the 5-methyl cytidine was dissolved in distilled water, and in series 6-10, the nucleoside was dissolved in physiological salt solution. In doses administered, series 4-5 overlapped with series 6-7. The number of mice that showed a regression of tumor increased in the successive series (48%-63% in series 1-5 and 25%-73% in series 6-10). As the number of mice with regressing tumors increased, the percentage of mice showing multiple primary tumors also increased. The administration of the nucleoside in physiological salt solution altered the inhibitory effect of 5-methyl cytidine on spontaneous tumors. For example, in physiological salt solution the 0.51 mg/injection gave as much inhibitory action as 1.03 mg/injection in distilled water. An inverse dose response is thus indicated between the amount of 5-methyl cytidine injected and the inhibition of spontaneous tumors in mice (percentage of regression and number of multiple primary spontaneous tumors are the criteria of inhibition considered).
Tumour-bearing mice, 248 in number, have been injected with 5-methyl-cytidine dissolved in physiological salt solution. The mice were divided into 5 series depending upon the amount of 5-methyl-cytidine they received. Mice of a successive series received 43.2, 28.8, 14.4 and 7.2 mg/kg body weight. There was a progressive increase in the percentage of mice showing regression of tumours in the successive series, as follows: 45%, 50%, 65%, 60%, and 67.8% respectively, giving an average percentage of regressions of 59.7%. The incidence of mice developing multiple primary tumours increased in the same successive series respectively as follows: 25%, 43.8%, 58.3%, 73.3%, and 70%, thus giving an average of 58.3%. The evidence obtained indicates an inverse correlation (dose-response) between the amount of the 5-methyl-cytidine injected and the percentage of regressions of spontaneous tumours.
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