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ÈòÁã¿¡¼­ N-butyl-N-(4-hydroxybutyl) Nitrosamine¿¡ ÀÇÇØ À¯¹ßµÈ ¹æ±¤¾Ï¿¡ ´ëÇÑ ¹æ±¤³» BCGÁÖÀÔÀÇ È¿°ú The Effects of Intravesical BCG Instillation on Bladder Cancer Induced by N-butyl-N-(4-hydroxybutyl) Nitrosamine

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Abstract

°á·Ð
ÀúÀÚ´Â BBNÀ¸·Î À¯¹ßµÈ Fisher 344 ÈòÁãÀÇ ¹æ±¤¾Ï ¸ðµ¨¿¡¼­ ¹æ±¤³» BCGÁÖÀÔÀÌ ¾Ï ¹ß»ý
¿¡ ¾î¶² ¿µÇâÀ» ¹ÌÄ¡´ÂÁö ¾Ë¾Æº¸°í NO »ý¼º¾ïÁ¦Á¦¸¦ Åõ¿©ÇÑ ±º µî¿¡¼­ ¿ä Áß NO´ë»ç¹°ÀÇ
¹è¼³Á¤µµ¿Í ¹æ±¤¾ÏÀÇ ¹ß»ýÀ², ¹ß»ýµÈ ¾ÏÀÇ ¼ö, Å©±â ¹× iNOSÀÇ ¹ßÇöÁ¤µµ¿¡ ´ëÇÑ ¿¬±¸¸¦ ½Ã
ÇàÇÑ °á°ú´Â ´ÙÀ½°ú °°´Ù.
1. ¿ä Áß nitrite¹è¼³Àº I±º(´ëÁ¶±º)¿¡ ºñÇÏ¿© II±º (BBN+BCG)¿¡¼­ ÀÇÀÇÀÖ°Ô Áõ°¡ÇÏ¿´À¸¸ç
(p<0.05), III±º (BBN+BCG+NGMMA)ÀÇ ¿ä Áß nitrite¹è¼³Àº (BBN+BCG)¿¡
ºñÇÏ¿© ÇöÀúÇÏ°Ô °¨¼ÒÇÏ¿´´Ù(p<0.05).
2. ¹æ±¤¾ÏÀÇ ¹ß»ýºóµµ¿¡ À־ °¢ ±º°£ÀÇ Â÷ÀÌ´Â ¾ø¾ú´Ù(p>0.05).
3. ¹ß»ýµÈ ¾ÏÀÇ ¼ö´Â I±º(´ëÁ¶±º)¿¡ ºñÇÏ¿© II(BBN+BCG)¿¡¼­ ÀÇÀÇÀÖ°Ô ÀûÀº ¼öÀÇ ¾ÏÀÌ ¹ß
»ýÇÏ¿´°í(p<0.05) III±º(BBN+BCG+NGMMA)¿¡¼­´Â B±º¿¡ ºñÇÏ¿© ¸¹Àº ¼öÀÇ
¾ÏÀÌ ¹ß»ýÇÏ¿´´Ù(p<0.05).
4. ¾ÏÁ¾ ¹ß»ý±º¿¡¼­ ¾ÏÀÇ Å©±â¿¡ ´ëÇÑ ºñ±³¸¦ ÇÏ¿´À»¶§ I±º(´ëÁ¶±º)Àº II±º(BBN+BCG)¿¡
ºñÇÏ¿© ¾ÏÀÇ Å©±â°¡ ÄÇÀ¸¸ç Åë°èÇÐÀûÀ¸·Î ÀÇÀÇ ÀÖ´Â °á°ú¸¦ º¸¿´´Ù(p<0.05). ¶ÇÇÑ III±º
(BBN)BCG+NGMMA)Àº I±º(´ëÁ¶±º), II±º(BBN+BCG)¿¡ ºñÇÏ¿© ¾ÏÀÇ Å©±â°¡
ÇöÀúÇÏ°Ô ÄÇ´Ù(p<0.05).
5. iNOS ¹ßÇö¾ç»óÀº II±º(BBN+BCG)°ú III±º(BBN+BCG+NGMMA)¿¡¼­´Â I
±º(´ëÁ¶±º)¿¡ ºñÇÏ¿© ÇöÀúÈ÷ Áõ°¡ÇÏ¿´°í, ´ëÁ¶±ºÀ» Á¦¿ÜÇÑ ³ª¸ÓÁö ±º¿¡¼­ÀÇ ÇöÀúÇÑ Â÷ÀÌ´Â
¾ø¾ú´Ù.
ÀÌ»óÀÇ °á°ú¸¦ Á¾ÇÕÇÏ¸é ¹æ±¤³» BCGÁÖÀÔ¿ä¹ýÀº 0.1% BBNÅõ¿©³óµµ¿¡ ÀÇÇÑ ¹æ±¤¾ÏÀÇ ¹ß»ý
ºóµµ¿¡´Â ¿µÇâÀÌ ¾ø¾úÀ¸³ª, ¹ß»ýµÈ ¾ÏÀÇ ¼ö ¹× Å©±â¸¦ ÀÇÀÇÀÖ°Ô °¨¼Ò½ÃÅ°´Â ¿µÇâÀÌ ÀÖ¾ú´Ù.
ÀÌ·¯ÇÑ BCGÀÇ Ç×Á¾¾çÈ¿°ú´Â ¿ä Áß nitriteÀÇ ¹è¼³·®ÀÌ BCGÅõ¿©±º¿¡¼­ Áõ°¡ÇÑ °ÍÀ¸·Î º¸¾Æ
¹æ±¤³» BCGÁÖÀÔ ÈÄ ¸é¿ª¹ÝÀÀÀ¸·Î »ý¼ºµÈ NOÀÇ Ç×Á¾¾çÈ¿°ú¿¡ ÀÇÇÑ °ÍÀ¸·Î »ç·áµÈ´Ù.
#ÃÊ·Ï#
Purpose: We investigate the effects of intravesical BCG therapy on the occurance of
superficial bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) in
Fisher 344 rats in vivo. We also examine whether NO mediated the antitumor activity
of BCG against superficial bladder cancer in Fisher 344 rats.
Materials and Methods: BBN(0.1%) is orally administered for 20 weeks and it is
combined with BCG(0.27mg) or NG-monomethyl-L-arginine (NG
MMA, 10mg). once every week from 8th week to 19th week. The rats are
sacrified at 20th week. NO secretion in urine for 24 ours is significantly increased in the
BCG treated rats compared to the animals treated with saline or NGMMA.
Results: Pathologic findings demonstrate that the incidence of carcinoma is not
statistically different in saline, BCG, NGMMA(p>0.05). However the size
and number of tumor is decreased in the BCG treated rats compared with saline or
NGMMA treated rats bearing bladder cancer induced by BBN(p<0.05).
Inducible NO synthase(iNOS) is strongly induced in bladder tissue of rats treated with
BCG and NGMMA but not in saline.
Conclusions: Intravesical instillation of BCG on bladder cancer induced by BBN does
not decrease the cancer occurrence but reduces the number and size of bladder cancer.
Our results suggest that nitric oxide induced by intravesical instillation of BCG may
mediate antitumor activity against the occupance of superficial bladder cancer.

Bacillus Calmette-Guerin; Nitric oxide; N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer NG<;

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