Effect of Experimental Ehrlich Ascites Tumors on Healing of Abdominal Wall Wounds in Mice
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Abstract: Many systemic factors may influence the healing process. The present study aimed to analyze histological modifications induced by the presence of Ehrlich ascites tumors on laparotomic surgical scars in BALB/c mice. A total of 52 mice were used. Half of the mice were injected with Ehrlich tumor cells, and 7 days later (day 7) all mice underwent laparotomy. On day 11, the scar was resected in 10 mice with the tumor and in the 10 control mice. The procedure was repeated on day 14 with the remaining animals. The scar tissue was histologically evaluated by means of semiquantitative analysis for acute inflammation, re-epithelization, formation of granulation tissue, chronic inflammation, fibroblast proliferation, and collagenization. Mice injected with tumor cells gained weight due to ascites growth. Histologic results showed that Ehrlich ascites tumor cells did not affect initial acute inflammation, re-epithelization, and formation of granulation tissue (P = ns). Chronic inflammation and fibroblast proliferation were, however, significantly decreased in mice with tumors, whereas collagenization had increased (P = 0.001). These results show that Ehrlich ascites tumors affect the healing process in mice. Despite a decrease in chronic inflammation and fibroblast activity, scars in these animals had more collagen, were more fibrous, and were better organized.
Address correspondence to:
Flávio Luiz L. Salgado, MD
Rua do Corrêa, 111, CEP: 12080-290
Taubaté, São Paulo, Brazil
Phone: +55-12-36212272
Email: f-salgado@uol.com.br
The Ehrlich tumor as described in 1906,1 originated from a murine breast carcinoma. It is one of the best characterized transplantable tumors as it may be maintained in solid or ascitic form, and is currently one of the most frequently used experimental models.2 The experimental Ehrlich ascites tumor establishes in 1 week and results in angiogenesis, cell proliferation, and invasion, which is similar to other neoplastic processes.
Healing is a process whereby injured tissue is replaced with scar tissue and is not dependent on the cause of the wound. It is now accepted that healing has 5 stages—an acute inflammatory process that proceeds through cell proliferation, formation of connective tissue, contraction, and finally wound remodeling.3–5 In both rats and mice, the inflammatory stage lasts 4 days, fibroplasia lasts 14 days, and maturation begins soon after.6
Currently, surgical procedures are based in notions of surgical metabolism, dietetic and anesthesia variables, and accurate surgical techniques, which aim to shorten surgical time and reduce trauma to avoid any effects on the healing process.7,8 The process may also be influenced by systemic factors that are intrinsic to the patient such as circulatory conditions, nutritional status, diabetes, and immunosuppression. Local factors related to the wound such as infection, early movement, presence of foreign bodies, and location, size, and wound type are also involved.
A patient with cancer will have the presence of systemic factors that possibly affect healing mechanisms within the various stages of the disease.
The objective of this work was to analyze histological alterations of laparotomy scars in mice induced by experimental Ehrlich ascites tumors and to determine if the neoplastic condition influences the healing process.
Materials and Methods
Fifty-two 2-month-old female BALB/c mice weighing between 18 g and 22 g were used in this study. The animals were weaned at day 20 and were maintained in individual cages in standard temperature and humidity conditions with a 12-hour light cycle. Food and water were interrupted at 6 hours and 1 hour, respectively, before submitting the animals to the surgical procedure.
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