Involvement of histamine in growth of mouse and rat tumors: antitumoral properties of monofluoromethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase.
Involvement of histamine in growth of mouse and rat tumors: antitumoral properties of monofluoromethylhistidine, an enzyme-activated irreversible inhibitor of histidine decarboxylase.
复制标题
组胺参与小鼠和大鼠肿瘤的生长：单氟甲基组氨酸的抗肿瘤特性，单氟甲基组氨酸是组氨酸脱羧酶的酶激活的不可逆抑制剂。
作者：
J. Bartholeyns;M. Bouclier
目前的研究表明，新合成的组胺参与了一些动物肿瘤的发展（例如，小鼠中的刘易斯肺癌和大鼠中的莫里斯肝癌）。接种后约1周，在肿瘤中观察到组氨酸脱羧酶（HDC）的显著诱导和组胺浓度的增加，并且鸟氨酸脱羧酶活性和多胺浓度平行增加。H2受体拮抗剂，西咪替丁，显着降低肿瘤生长的动物模型，而H1受体拮抗剂，右氯苯那敏，没有效果，表明组胺可以通过H2受体网站。通过局部注射化合物48/80诱导的肿瘤组胺的广泛消耗没有导致显著的细胞抑制作用。单氟甲基组氨酸（MFH），一种酶激活的不可逆的HDC抑制剂，延缓了培养中生长的肝癌组织培养细胞的生长，并且当s.c.在60 mg/kg/天剂量下，它极大地抑制了i.m.通过肝癌组织培养细胞在布法罗大鼠。MFH对小鼠EMT 6肉瘤和刘易斯肺癌也有明显的抗肿瘤作用，这与抑制HDC和耗尽肿瘤中的组胺含量有关。当MFH与特异性鸟氨酸脱羧酶抑制剂DL-α-二氟甲基鸟氨酸联合治疗时，这些细胞抑制作用明显增强。该组合的抗肿瘤作用与肿瘤组织胺和腐胺含量的显着降低有关。有人提出，新生组胺，新合成的腐胺和亚精胺一样，在动物肿瘤的快速增殖中起作用。通过基本无毒的药物如MFMH抑制HDC可能代表控制肿瘤生长的新方法。
The present study suggests that newly synthesized histamine is involved in the development of some animal tumors (e.g., Lewis lung carcinoma in mice and Morris hepatoma in rats). A marked induction of histidine decarboxylase (HDC) and an increase in the histamine concentration were observed in the tumors approximately 1 week after inoculation, and there were parallel increases in ornithine decarboxylase activity and the concentrations of polyamines. The H2 receptor antagonist, cimetidine, significantly reduced tumor growth in the animal models while the H1 receptor antagonist, dexchlorpheniramine, had no effect, suggesting that histamine could act via H2 receptor sites. Extensive depletion of tumor histamine induced by local injection of Compound 48/80 did not result in a significant cytostatic effect. Monofluoromethylhistidine (MFMH), an enzyme-activated irreversible inhibitor of HDC, retarded the growth of hepatoma tissue culture cells grown in culture, and when infused s.c. at 60 mg/kg/day it greatly inhibited the development of tumors induced i.m. by hepatoma tissue culture cells in Buffalo rats. MFMH also had pronounced antitumoral effects on EMT6 sarcomas and Lewis lung carcinomas in mice, which were associated with inhibition of HDC and depletion of the histamine content of the tumors. These cytostatic effects were clearly enhanced when MFMH was combined in therapy with the specific ornithine decarboxylase inhibitor, DL-alpha-difluoromethylornithine. The antitumoral effects of the combination were associated with marked decreases in the tumor histamine and putrescine contents. It is proposed that nascent histamine, like newly synthesized putrescine and spermidine, plays a role in the rapid proliferation of animal tumors. Inhibition of HDC by essentially nontoxic drugs such as MFMH could represent a novel approach to the control of neoplastic growth.
影响因子：
2.9
作者：
Cox,C;Mukerjee,S;Jackson,M;Dey,SK
通讯作者：
Dey,SK