Combination chemotherapy with 5-fluorouracil (5FU) and 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) prolongs survival of rats

نویسندگان

  • M DANZI
  • J P CRUSE
  • C G CLARK
چکیده

The effects of combination chemotherapy with 5FU and BCNU on rats with dimethylhydrazine (DMH)-induced colon cancer were investigated in a long term survival study. Eighty Wistar rats received a colon cancer producing regimen on DMH (40 mg/kg body weight/week, subcutaneously for 10 weeks). After presenting with signs of colonic disease, all rats underwent diagnostic laparotomy and colonoscopy when colon tumours were located, measured and the extent of the disease staged. Only animals with tumours (n=63) were included and allocated to one of three tumour stages. Stage A (n=17), had colonic tumours without serosal involvement; stage B (n=28) had serosal involvement without metastases; stage C (n= 18) had serosal involvement with lymphadenopathy and/or metastases. Each group was randomly allocated into two subgroups, one serving as untreated controls while the other received 5FU (300 mg/m2 weekly intragastrically for life) together with BCNU (40 mg/m2 intraperitoneally on days 0, 42 and 84). The effect of chemotherapy on tumour growth was measured sequentially by colonoscopy. Animals were observed until death and necropsied, when colon carcinoma was histologically confirmed and survival analysed. The results indicate that chemotherapy significantly prolongs the survival of rats with the least advanced disease (stage A) but was of no benefit to rats with locally advanced or metastatic disease (stages B and C). Furthermore, chemotherapy was associated with a significant reduction in tumour size. Survival analyses in untreated animals show that the laparotomy staging system adopted provides accurate prognostic information. This study shows that DMH-induced colon tumours are chemosensitive, and suggests that this animal model may be a valuable testing ground for new chemotherapeutic agents.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Combination chemotherapy with 5-fluorouracil (5FU) and 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) prolongs survival of rats with dimethylhydrazine-induced colon cancer.

The effects of combination chemotherapy with 5FU and BCNU on rats with dimethylhydrazine (DMH)-induced colon cancer were investigated in a long term survival study. Eighty Wistar rats received a colon cancer producing regimen on DMH (40 mg/kg body weight/week, subcutaneously for 10 weeks). After presenting with signs of colonic disease, all rats underwent diagnostic laparotomy and colonoscopy w...

متن کامل

Mutational specificities of 1,3-bis(2-chloroethyl)-1-nitrosourea and nitrogen mustard in the SUP4-o gene of Saccharomyces cerevisiae.

A collection of 346 mutations arising in the SUP4-o gene of the yeast Saccharomyces cerevisiae following treatment with 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) or nitrogen mustard was analyzed by DNA sequencing. Both agents induced all possible types of base-pair substitution as well as deletions and double mutations. The base-pair changes consisted primarily of events at G.C pairs and wer...

متن کامل

Responses of cycling and noncycling cells to 1,3-bis(2-chloroethyl)-1-nitrosourea and to bleomycin.

The current literature contains conflicting data on the response of cycling and noncycling cells to 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and to bleomycin (BLEO). Such data may be important for the design of multiple drug protocols for the treatment of solid cancers and we therefore reinvestigated these responses. After exposure to graded doses of BCNU, the survival curves of exponentiall...

متن کامل

NOICM-43784with the Divisionof Cancer Treatment, National Cancer

N,N'-Bis(2-chloroethyl)-N-nitrosourea (BCNU) is a sub strate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1,3-bis(2-chloro ethyl)urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competiti...

متن کامل

Glutathione content and glutathione-S-transferase expression in 1,3-bis(2-chloroethyl)-1-nitrosourea-resistant human malignant astrocytoma cell lines.

gamma-L-glutamyl-L-cysteinylglycine (GSH) has been shown to inactivate 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and quench DNA crosslink precursors of BCNU. Because of the central role of 2-chloroethyl-nitrosoureas in brain tumor chemotherapy, we investigated the intracellular GSH content and the expression of specific glutathione-S-transferases (GSTs) in three human malignant astrocytoma ce...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2006