Induction of invasive and experimental metastasis potential in BALB/c 3T3 cells by benzo(a)pyrene transformation.
A clone of BALB/c 3T3 cells (A-31), which is highly resistant to spontaneous in vitro transformation, was treated with the carcinogen benzo(a)pyrene [B(a)P]. This agent was capable of inducing in vitro transformation in the presence of S9 activating system and 6 weeks after treatment large foci were detected. Transformation frequency in solvent control groups was very low. Three foci from a single plate of two different experiments were pooled and the cells tested for their in vitro invasive properties and in vivo tumorigenic and metastatic potential. B(a)P-transformed 3T3 cells grew in soft agar and were highly tumorigenic when injected s.c. in nude mice (75% incidence within 7 weeks). Untreated cells were poorly tumorigenic (0/4 mice had tumors within 7 weeks), though they also gave rise to neoplasms after a longer latency. Spontaneous metastasis incidence was low for both controls and treated cells; however, almost all animals (15/16) injected i.v. with B(a)P-transformed cells had pulmonary nodules in the experimental metastasis assay. A few nodules in some of the animals in the control group were detected (4/16). B(a)P-transformed cells were able to invade a thin coating of matrigel in the chemoinvasion assay and also grew in matrigel showing an invasive, branching morphology. Untreated cells did not grow or invade. Our data suggest that a single treatment with a chemical carcinogen can increase tumorigenicity as well as confer invasive and experimental metastasis potential in BALB/c 3T3 cells. This work provides evidence for a role of chemical carcinogens in tumor progression.
Melchiori
A
A
Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Colacci
A
A
Lollini
P L
PL
De Giovanni
C
C
Carlone
S
S
Grilli
S
S
Parodi
S
S
Albini
A
A
D016475:3T3 Cells; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis; D002999:Clone Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation
D001564:Benzo(a)pyrene