2012
Increased concentration of metronidazole and its hydroxyl metabolite in colon cancer in women
"In the study, we found a differential (not statisti cally significant) concentration of MTZ in colorectal cancer and surrounding healthy tissue, probably due to greater absorption and accumulation of the chemotherapeutic in carcinoma vs. non-affected tissue. Absorption as well as accumulation of metronidazole may depend on the tumor size and its morphological structure. However, we noted approximately the same tumor size in all patients. Larger necrotic tumors due to increased hypoxia may absorb greater amounts of the drug, which may explain increased (tendency) concentration.
Patients after resection of colon cancer receive MTZ to avoid complications caused by infections. Metronidazole and its metabolite MTZOH
can be accumulated in tissues with low redox status and
probably in metastatic cells. On the basis of the MTZ carcinogenic potential and the
unknown MTZOH activity in tumor,
it can be assumed that metronidazole
may enhance the invasiveness of cancer. The results of our study
may suggest that women are more exposed to such an effect of metronidazole than man."
http://www.if-pan.krakow.pl/pjp/pdf/2012/5_1276.pdf
1988
Cancer After Exposure to Metronidazole
We assessed the risk of occurrence of cancer associated with exposure to metronidazole in the 771 female residents of Rochester, Minnesota, who were treated with metronidazole for vaginal trichomoniasis during the period 1960 through 1969 and were followed up for a total of 12,628 person-years. Standardized morbidity and mortality ratios were determined by using an expected number calculated by applying age-specific incidence rates from Rochester studies and Cancer Surveillance, Epidemiology, and End-Results Reporting (SEER) data to the person-years of follow-up. The overall standardized morbidity ratios for cancer at all sites were 1.4 (Rochester, 1978 through 1983), 1.5 (SEER data for Iowa, 1978 through 1981), and 1.2 (SEER data for Connecticut, 1978 through 1981). By site of the cancers, the standardized morbidity ratios greater than unity were those for malignant lesions of the lung, breast, thyroid, bladder, brain, kidney, nasopharynx, and oral cavity, as well as for multiple myeloma and malignant melanoma; however, the only significantly elevated standardized morbidity ratio was that for bronchogenic carcinoma. After adjustment for smoking status, the standardized morbidity ratio for bronchogenic cancer was 2.5 (95% confidence interval of 1.3 to 4.4). The standardized mortality ratio for cancer at all sites was 1.4 (95% confidence interval of 0.9 to 2.2). The analysis of these data suggests
no significant increase in cancer-related morbidity or mortality for women exposed to metronidazole for treatment of vaginal trichomoniasis.
http://www.mayoclinicproceedings.org/article/S0025-6196(12)64947-7/fulltext
2009
Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole
“A distinguishing property among the three compounds is their reduction potential. The 5-nitroimidazol derivative (MTZ) shows comparatively low reduction potential: it can be reduced to the corresponding amino derivative only under anaerobic conditions and its spectrum of activity can result limited to anaerobic or facultative anaerobic bacteria. On the other hand, both the antitrypanosomal drugs, NFX and BNZ, may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells by the formation of free radicals and redox cycling.
In conclusion, the genotoxic profile of MTZ, NFX, and BNZ is further defined from our findings. MTZ therapeutic use could represent a genotoxic hazard only for the host cells in anoxic conditions. The high DNA damaging potential of NFX and BNZ on mammalian cells, together with other known severe side-effects on patients and low effectiveness in the second stage of the Chagas’ disease, call for new safer drugs against Trypanosoma infection.”
http://www.hindawi.com/journals/jpr/2009/463575/