Effect of varying the onset of exposure to DDT on its modulation of AFB1-induced hepatocarcinogenesis in the rat.
We have previously reported that p,p'-dichlorodiphenyl-trichloroethane (DDT) inhibited the hepatocarcinogenicity of aflatoxin B1 (AFB1) if given to rats 1 week prior to AFB1 but could enhance the carcinogenesis when given 1 week after the completion of AFB1 treatment. However, simultaneous administration of DDT with AFB1 resulted in a slight reduction in the incidence of liver tumours. In the present experiment in which the dose of AFB1 was reduced to about half of that used previously, we observed that DDT markedly inhibited the hepatocarcinogenesis if given to animals starting at the same time with AFB1. On the other hand, giving DDT to animals starting in the middle of AFB1 treatment resulted in a significant enhancement of hepatocarcinogenesis. DDT exhibited a maximal tumour promoting effect when given either 1 or 3 weeks after completion of AFB1 treatment. It enhanced the number of animals bearing liver carcinomas as well as the number of carcinomas per animal. Determination of gamma-glutamyltranspeptidase in the serum revealed that the activity increased only in animals bearing big and/or a number of carcinomas in the livers especially in those promoted by DDT. These results therefore demonstrated that DDT will act as an inhibitor of AFB1-induced hepatocarcinogenesis if it is given to animals starting either prior to or at the same time as carcinogen. On the other hand, it will act as a tumour promoter if given to animals starting either in the middle of or after the completion of AFB1 treatment.
Rojanapo
W
W
Biochemistry and Chemical Carcinogenesis Section, National Cancer Institute, Bangkok, Thailand.
Kupradinun
P
P
Tepsuwan
A
A
Tanyakaset
M
M
D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D003043:Cocarcinogenesis; D003634:DDT / Q000008:administration & dosage* / Q000633:toxicity; D004121:Dimethyl Sulfoxide; D004334:Drug Administration Schedule; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood
D016604:Aflatoxin B1; D003634:DDT; D005723:gamma-Glutamyltransferase; D004121:Dimethyl Sulfoxide