Summary Increased understanding of the molecular basis of colorectal cancer and recognition that extracellular DNA circulates in the plasma and serum of cancer patients enables new approaches to detection and monitoring. We used a polymerase chain reaction (PCR) assay to demonstrate mutant K-ras DNA in the plasma or serum of patients with colorectal cancer. Plasma or serum was fractionated from the blood of 31 patients with metastatic or unresected colorectal cancer and from 28 normal volunteers. DNA was extracted using either a sodium chloride or a gelatin precipitation method and then amplified in a two-stage PCR assay using selective restriction enzyme digestion to enrich for mutant K-ras DNA. Mutant K-ras DNA was detected in the plasma or serum of 12 (39%) patients, all confirmed by sequencing, but was not detected in any of the normal volunteers. K-ras mutations were detected in plasma or serum regardless of sex, primary tumour location, principal site of metastasis or proximity of chemotherapy and surgery to blood sampling. Tumour specimens available for 19 of the patients were additionally assayed for ras mutations and compared with blood specimens. Our results indicate mutant K-ras DNA is readily detectable by PCR in the plasma or serum of patients with advanced colorectal cancer. Thus, plasma-or serum-based nucleic acid amplification assays may provide a valuable method of monitoring and potentially detecting colorectal cancer.
Acrylamide is oxidized by cytochrome P450 2E1 (CYP2E1) to its epoxide form, glycidamide, which is believed to be responsible for the mutagenic and carcinogenic activities. This study was carried out to investigate the early changes that may be related to the carcinogenic activity of acrylamide in thyroid, adrenal glands and testis in male rats. Forty adult Sprague Dawley male rats were divided equally into four groups, rats of Group I served as control, and rats of Groups II, III and IV were treated orally with acrylamide with doses 5, 10, 15 mg/kg/day body weight for 8 weeks. The results indicated that the plasma carcino embryonic antigen (CEA) and malondialdehyde (MDA) levels are higher, but free and total testosterone, triiodothyronine (T(3)) and thyroxine, or 3,5,3',5'-tetraiodothyronine (T(4)) and corticosterone levels are lower in rats treated with acrylamide than that in control rats. This study provides evidence of endocrine disturbance to the testis, thyroid and adrenal glands, which are also the organs in which acrylamide has been shown to cause tumors in experimental animals.
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