Effects of Partial Hepatectomy on the Growth Characteristics and Hypoxic Fractions of Xenografted DLD-2 Human Colon Cancers

Abstract

A recent publication by Leith et al. (Cancer Res. 51, 4111-4113, 1991) showed that administration of epidermal growth factor (EGF) (0.25 mg/kg; q.i.d. x 7) to mice bearing xenografted A431 human epidermoid cancers produced increased tumor growth and a reduction of the percentage of hypoxic cells within neoplasms. In contrast, sialoadenectomy, which removes the majority of circulating EGF in the mouse, resulted in slower tumor growth and increased hypoxic percentages. To investigate such homeostatic mechanisms further, we investigated the growth characteristics and hypoxic fractions of xenografted DLD-2 human colon tumors when tumor-bearing mice received partial hepatectomy (about 65%), unilateral nephrectomy, or nonspecific surgical trauma (laparotomy). Surgical procedures were performed when tumor volumes were about 375 mm3, and hypoxic percentages within tumors were measured by clonogenic excision assay procedures 72 h later. We found that partial hepatectomy increased the growth rates of the transplanted DLD-2 cancers by about a factor of 2.4. This increased growth rate was accompanied by an increase in the mitotic index from about 1.5 to 3.0%. Also, hypoxic fractions were decreased from 0.561 in control tumors to 0.235 in tumors from mice receiving partial hepatectomies. Unilateral nephrectomy and nonspecific surgery manipulations did not alter tumor growth rates, mitotic indices, or hypoxic percentages. These results indicate that partial hepatectomy produces significant alterations in tumor physiology. Results are consistent with a growth factor-mediated mechanism.