수종 마우스임파종의 발육에 대한 성홀몬의 효과 : 특히 발정물질의 Gardner 6C3HED 임파육종 발육촉진효과에 대하여

Abstract

[영문]

Experimental studies and clinical observations accumulated during the last several decades clearly indicate that endocrine factors play an important role in initiation and subsequent growth of neoplasms. Estrogenic hormone has been proved to be carcinogenic by various investigators. However, little has been known of the effect of hormones on the growth of neoplasms. A number of induced or spontaneous neoplasms have been tested, but the results are controversial, if not satisfactory. Nevertheless, it is well known that some estrogen induced tumors(testicular, pituitary, and mammary) of the mouse are "conditional neoplasms" and dependent upon estrogenic hormone for growth after transplantation; the recipient must be estrogen-treated if implants are to grow progressively. Certain mammary tumors of mice, although they might be malignant, are still dependent. The effect of cortisone or ACTH on the growth of mouse lymphomas has been well studied, but no study has so far made on the possible relationship between sex hormones and the growth.

In the experiments here summarized, the effects of sex hormones on the growth of several mouse lymphomas have been studied. and the observation has been made that the growth of 6C3HED and Law lymphoma cells transplanted in hosts given estrogenic hormones is regularly enhanced. Furthermore, these tumor cells, implanted in alien hosts given estrogenic hormone, grew progressively until the host animals died.

whereas they regressed following a transient period of growth in untreated alien mice. In addition, some striking observations made on the relation between estrogenic hormone and the inhibitory effects of guinea pig serum on the growth of 6C3HED lymphosarcoma cells are also recorded.

General Plan of Experiments-Malignant lymphoma cells of any of six kinds(Gardner's lynphosarcoma 6C3HED, IRG and Neo RG, Law's lymphoma. Lymphoma L-1210 and E-9514) were suspended in known numbers in a buffered glucose Ringer solution, then implanted subcutaneously in both groins of experimental animals in which the cells were known to grow (the first three lymphosarcomas and lymphoma E-9514 in ZBC mice. Law's lymphoma in AKR mice, and lymphoma L-1210 in DBA/2 mice); in other experiments in alien hosts. lymphosarcoma 6C3HED was implanted in either AKR or Swiss mice. Lymphosarcomas IRG and Neo RG, Law's lymphoma and lymphoma L-1210 in Swiss mice, and lymphoma E-9514 in AKR mice. Some implanted animals were given subcutaneous injections of various hormones before or after implantation, while others were kept untreated as controls, and still others wore given subcutaneous injections of sesame oil. In some experiments, normal guinea pig serum was given intraperitoneally, in single or repeated doses, in animals given estrogenic hormone and in the untreated control group, or in non-pregnant female and in pregnant mice carrying with them 6C3HED lymphosarcoma. The outcome of the implantations and injections was followed by repeatedly observing and gently

palpating the groins of the injected animals, with careful and frequent chartings to show the size and course of every tumor that developed.

The experimental results may be summarized as follows.

1. Estrogenic hormone regularly enhanced the growth of subcutaneously transplanted 6C3HED lymphosarcoma cells. In ZBC mice(susceptible strain) given either diethylstilbestrol or estradiol, the tumors grew faster, the tumor masses being larger (2-3 times) and firmer, and the hosts succumbing 5-8 days earlier than those in untreated control mice.

2. The 6C3HED lymphosarcoma cells implanted in untreated control ZBC mice regressed promptly following three daily intraperitoneal injections of normal guinea pig serum beginning nine days after implantation, all animals remaining lively and devoid of palpable tumors until 31 days after implantation when the animals were killed. However, in mice given iethylstilbestrol (8 mg. twice on the day of implantation), the tumors regressed only temporarily following the administration of guinea pig serum, but resumed growth, enlarged progressively, and all hosts died within 29 days after implantation.

3. When 6C3HED lymphosarcoma cells were implanted in 8 male and 8 female untreated AKR mice(alien hosts), the tumors grew for a while and thereafter regressed completely within 16 days after implantation, all animals remaining lively and devoid of palpable tumors until 21 days after implantation, when the animals were killed, except for one male mouse; in this mouse, the tumors regressed, but palpable tumors still remained by this time. By contrast, in the same number of male and female mice given diethylstilbestrol (four daily

subcutaneous injections of 2.5 mg beginning 3 days before implantation), the tumors

enlarged progressively, and all hosts succumbed within 27 days after implantation, except for one female mouse which remained alive with huge tumors in both groins until the present.

4. The growth of guinea pig serum-resistant strains of 6C3HED lymphomas (IRG and Neo RG) cells in ZBC mice was similarly enhanced by the administration of diethylstilbestrol to hosts carrying the tumors, as was the growth in the non-resistant strain. This result suggest that the susceptibility of 6C3HED lymphosarcoma cells to guinea pig serum is not related to the susceptibility of these tumor cells to estrogenic hormone.

5. The growth of Law's lymphoma cells implanted in AKR mice (native hosts) was also enhanced by diethylstilbestrol, the result indicating that 6C3HED lymphosarcoma ia not the only tumor the growth of which is enhanced by estrogenic hormone.

6. When tumor cells were implanted in alien hosts given diethylstilbestrol, the growth of 6C3HED lymphosarcoma cells was noticeably prolonged in all mice tested; but growth of Neo RG lymphosarcoma cells was enhanced in 62.5%, Law's lymphoma cells in 35%, and lymphomas L-1210 and E-5514 cells in none of the mice tested, as compared to the growth of various lymphoma cells in untreated control mice.

Although both 6C3HED Lymphosarcoma and Law's lymphoma cells responded to diethylstilbestrol, the enhanced growth of 6C3HED lymphosarcoma cells in hosts

given estrogenic hormone appears highly specific, judging from the regularity of the enhanced growth observed.

7. Testosterone to far demonstrated no appreciable effects on the growth of 6C3HED, IRG or on Law'S lymphoma cells implanted in native hosts.

8. Frogesterone influenced in no way the growth of 6C3HED, Law or L-1210 lymphoma

cells implanted in alien hosts.

9. When normal guinea pig serum was given intraperitoneally shortly before delivery, it exhibited almost no inhibitory effects on the growth of 6C3HED lymphosarcoma cells in pregnant mice with only one exception among 27 pregnant mice tested.

10. The serums obtained from guinea pigs which received repeated daily subcutaneous injections of diethylstilbestrol also exhibited almost no inhibitory effects on the growth of 6C3HED lymphosarcoma cells.

The results of the experiments herein summarized suggest that 6C3HED lymphosarcoma is malignant and yet may be a hormone-dependent tumor. like certain mammary tumors of mice. Besides, the last two results indicated that the inhibitory effects of guinea pig serum on 6C3HED lymphosarcoma cells are powerfully interfered with by estrogenic hormone or by endocrine derangements of the host animals resulting from excessive estrogenic hormone.