氮芥抗药性人早幼粒白血病HL60细胞亚系的建立及其生物特性

用逐步递增药物浓度和软琼脂细胞克隆技术，药物连续作用１４个月后获得氮芥（ＨＮ２）抗药性人早幼粒白血病ＨＬ６０细胞亚系，抗件达５～７倍（ＨＬ６０／ＮＨ２６），在无ＨＮ２培养液中５倍以上抗性维持１０个月以上，抗性细胞亚系的生物学特性除倍增时间稍长和克隆形成率略低外其生长曲线，细胞周期细胞ＤＮＡ指数，形态学，组织化学和染色体分析均与亲代细胞相似。     

The treatment of sulphur mustard burns with laser debridement.

The chemical warfare agent, sulphur mustard (SM), is a potent blistering agent in man. Skin exposure can produce partial-thickness burns which take up to three months to heal. The aim of this study was to investigate the use of early laser ablation as a means of accelerating this exceptionally slow rate of healing. Four circular partial-thickness SM burns were induced on the dorsum of nine large white pigs (under general anaesthesia). At 72 h post-exposure, three burns per animal were ablated with a single pass of an UltraPulse 5000C CO(2) laser, at a fluence of 5-6 J cm(-2). All the burns were dressed with silver sulphadiazine and a semi-occlusive dressing. At one, two and three weeks post-surgery three animals were culled and all lesions excised for histological analysis. Burn depth was confirmed and measurements of the radii of regenerative epithelium were performed allowing the area of the zone of re-epithelialisation in each lesion to be calculated. Laser-treated lesions showed a significant increase (350%) in healing rates compared to controls (p<0.005). At two weeks, the laser-treated sites were 95% healed in comparison with control sites (28% healed). These data suggest that laser ablation may be effective in the treatment of partial-thickness SM-induced skin injury.     

Chlorocarbamate-mustard-linked 1,1,2-triphenylbut-1-enes with a selective antitumor activity on mammary tumors containing estrogen receptors

Summary A 1,1,2-triphenylbut-1-ene with a 4-OH group at one C-1 phenyl ring and a chlorocarbamate mustard moiety at the second C-1 ring (compound 3) was synthesized in order to obtain a cytotoxic estrogen with a specific antitumor effect on estrogen-receptor-containing tumors. This compound was tested in comparison to the carrier (compound 1) and a compound (2) having a carbamate mustard group on both C-1 phenyl rings. The estrogen receptor affinity of compound 3 was only about one-quarter lower than that of compound 1, but much higher than that of compound 2. Compounds 2 and 3 showed only partially irreversible binding to the receptor owing to their relatively low alkylating properties. The growth inhibition of the receptor-positive MCF-7 breast cancer cell line by compound 3, but not by compound 1 or 2, was more pronounced than the inhibition of the receptor-negative line MDA. In vivo the hormone-dependent, transplantable mammary tumor MXT M3.2 of the mouse was much better inhibited by compound 3 than its hormone-resistent line MXT OVEX. Compounds 1–3 had no antiestrogenic properties in the mouse, but estrogenic activity was in the order 1>3>2. From these results and because the antitumor activity of compound 3 was superior to that of compounds 1 and 2 in the hormone-dependent tumor models, a selective, receptor-mediated cytotoxic effect of compound 3 on estrogen-receptor-positive tumors in obvious.Supported by the Deutsche Forschungsgemeinschaft, SFB 234 and the Matthias Lackas StiftungDedicated to Prof. Dr. M. F. El Etreby on the occasion of his 50th birthday     

Activity of the human carcinogen MeCCNU in the mouse bone marrow micronucleus assay

The nitrosourea mustard MeCCNU is the most recent organic chemical to be classified as a human carcinogen by IARC. MeCCNU gave a strong positive response when tested in the mouse bone marrow micronucleus assay. Activity was evident using either ip injection or oral gavage of the test chemical. These results further support the correlation between human carcinogens and their genotoxicity.     

唯地息眼凝胶剂治疗兔芥子气角膜损伤

目的:观察唯地息眼凝胶剂对兔芥子气角膜上皮损伤的治疗作用。方法:新西兰白兔8只,用200μL/L液态芥子气致伤双眼角膜5min,左眼为治疗组,用唯地息眼凝胶剂点眼,4次/d,右眼为对照组,用2.5g/L氯霉素眼液滴眼,4次/d,分别于染毒后2,8,16,24,36,48和72h对角膜荧光素着色区拍照,计算其上皮愈合速率和上皮破损率。结果:治疗组和对照组的角膜上皮愈合速率分别为(1.15±0.19)mm2/h和(1.03±0.12)mm2/h,两者有显著差异(P<0.05),角膜上皮破损率分别为44.4%和54.2%,两者差异显著(P<0.05)。结论:唯地息眼凝胶剂能促进芥子气染毒引起的兔眼角膜损伤的上皮愈合,也能减少角膜上皮反复破损。     

Nitrogen mustard gel-induced inflammation triggers lymphomatoid papulosis in patients with mycosis fungoides

Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30⁺ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8 months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30⁺ LPD.     

术中膀胱黏膜下注射盐酸氮芥、术后即刻丝裂霉素灌注化疗预防膀胱癌复发

目的探讨经尿道膀胱肿瘤电切(TUR-Bt)术中膀胱黏膜下注射盐酸氮芥、术后即刻丝裂霉素(MMC)膀胱灌注化疗预防膀胱癌复发的疗效。方法 112例行TUR-Bt术的膀胱癌患者随机分为2组,对照组56例:行TUR-Bt术后1周给予MMC常规膀胱灌注化疗;治疗组56例:TUR-Bt术中经尿道行膀胱黏膜下注射盐酸氮芥,术后再即刻行MMC膀胱灌注化疗,术后1周再给予MMC常规膀胱灌注化疗。比较观察2组患者术后3、6、12、18、24个月的复发情况。结果治疗组术后3、6、12、18、24个月的复发率低于对照组,比较差异有统计学意义(P<0.05)。结论 TUR-Bt术中膀胱黏膜下注射盐酸氮芥、术后即刻行MMC膀胱灌注化疗能显著提高膀胱癌治疗效果,减少术后复发,且无明显毒副反应。     

芥子气致肝脾损伤的研究现状

芥子气(SM)是一种战争中常用的化学毒剂,其致死、致伤率高,且伴随长期慢性伤害。其液气态可能损伤人体不同部位(如,呼吸道、皮肤、眼部等),近年来,SM损伤肝脾也备受人们关注。本文结合SM的毒理特征,对其造成肝、脾损伤的有关问题作一综述。     

Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis

Preclinical and clinical studies show that gastrointestinal (GI) inflammation can evoke sensory changes occasionally far from the original inflammatory site. Animal models of colitis with either trinitrobenzenesulphonic acid (TNBS) or mustard oil (MO) produce distinct patterns of somatic and visceral sensory changes. We evaluated the effects of four doses of i.v. vincristine 150 μg kg^?1 (total of 600 μg kg^?1) treatment on the somatic (thermal nociceptive threshold) and colonic (morphological) changes induced by TNBS or MO in rats. TNBS and MO groups were further submitted to vincristine or saline pretreatments. TNBS induced somatic hypersensitivity, while MO induced somatic hyposensitivity (P < 0.05) when compared to the saline and ethanol control groups. Vincristine per se induced somatic hypersensitivity (P < 0.05). This effect was enhanced by TNBS and reversed by MO treatments. Although vincristine increased the colitis area (colonic weight length^?1 ratio) and the Morris' score in TNBS‐treated rats, it did not alter the colitis area and even lowered the Morris' score in MO‐treated rats. Compared to the saline (control) group, vincristine did not alter the colonic microscopic pattern. However, such lesions scores are higher (P < 0.05) in colitis groups induced by TNBS and MO, pretreated or not with vincristine. In conclusion, the somatic changes induced by different models of experimental colitis are diverse and modulated differently by vincristine.