The effect of 1/3 partial hepatectomy on the growth of glutathione S-transferase positive foci.

Abstract

Our previous studies indicated that glutathione S-transferase 7-7 (GST 7-7) positive foci induced after initiation have a lower threshold towards proliferative stimuli compared with surrounding hepatocytes. This observation would predict that persistent growth stimuli of low intensity could be very effective in promoting the emergence of focal lesions. To test this possibility, the present study was designed to determine the effect of 1/3 partial hepatectomy (PH) on the incidence and growth of foci in initiated rat liver. The rationale for using a 1/3 PH was that it is known to induce a proliferative response which is less intense but more prolonged compared with that elicited by 2/3 PH. Male Fischer 344 rats (110-120 g) were initiated with diethylnitrosamine (200 mg/kg, i.p.). Three weeks later 1/3 PH (median lobe), 2/3 PH (median and left lobes) or sham operation (SH) was performed. An additional group of initiated animals had the median lobe and the left lobe of the liver removed sequentially (1/3 + 1/3 PH), 3 weeks apart. All rats were killed 8 weeks after carcinogen administration. The results indicated that the number of GST 7-7 positive foci was similar in all groups; however, the percent area occupied by foci was increased in rats receiving 2/3 PH compared with SH (0.21 +/- 0. 08 versus 0.09 +/- 0.03). Interestingly, 1/3 PH was nearly as effective as 2/3 PH in stimulating the growth of foci (percent area 0.18 +/- 0.06 versus 0.21 +/- 0.08), although the magnitude of the stimulus is only half for the former group compared with the latter; peak labeling index was 19 +/- 6 with 1/3 PH compared with 40 +/- 2 with 2/3 PH. Moreover, the maximum increase in the size of foci (percent area 0.37 +/- 0.12) was achieved when the median and left lobes were removed sequentially, three weeks apart. These results indicate that persistent growth stimuli of low intensity can be very effective in promoting the growth of focal lesions.